SpringerLink
Log in

Collagen biology making inroads into prognosis and treatment of cancer progression and metastasis

  • Published:
Cancer and Metastasis Reviews Aims and scope Submit manuscript

Abstract

Progression through dissemination to tumor-surrounding tissues and metastasis development is a hallmark of cancer that requires continuous cell-to-cell interactions and tissue remodeling. In fact, metastization can be regarded as a tissue disease orchestrated by cancer cells, leading to neoplastic colonization of new organs. Collagen is a major component of the extracellular matrix (ECM), and increasing evidence suggests that it has an important role in cancer progression and metastasis. Desmoplasia and collagen biomarkers have been associated with relapse and death in cancer patients. Despite the increasing interest in ECM and in the desmoplastic process in tumor microenvironment as prognostic factors and therapeutic targets in cancer, further research is required for a better understanding of these aspects of cancer biology. In this review, published evidence correlating collagen with cancer prognosis is retrieved and analyzed, and the role of collagen and its fragments in cancer pathophysiology is discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Germany)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Frantz, C., Stewart, K. M., & Weaver, V. M. (2010). The extracellular matrix at a glance. Journal of Cell Science, 123(24), 4195–4200. https://doi.org/10.1242/jcs.023820.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Gumbiner, B. M. (1996). Cell adhesion: the molecular basis of tissue architecture and morphogenesis. Cell, 84(3), 345–357. https://doi.org/10.1016/s0092-8674(00)81279-9.

    Article  PubMed  CAS  Google Scholar 

  3. Katsumi, A., Orr, A. W., Tzima, E., & Schwartz, M. A. (2004). Integrins in mechanotransduction. The Journal of Biological Chemistry, 279(13), 12001–12004. https://doi.org/10.1074/jbc.R300038200.

    Article  PubMed  CAS  Google Scholar 

  4. Engler, A. J., Sen, S., Sweeney, H. L., & Discher, D. E. (2006). Matrix elasticity directs stem cell lineage specification. Cell, 126(4), 677–689. https://doi.org/10.1016/j.cell.2006.06.044.

    Article  PubMed  CAS  Google Scholar 

  5. Walker, C., Mojares, E., & del Río Hernández, A. (2018). Role of extracellular matrix in development and cancer progression. International Journal of Molecular Sciences, 19(10). https://doi.org/10.3390/ijms19103028.

  6. Ricard-Blum, S. (2011). The collagen family. Cold Spring Harbor Perspectives in Biology, 3(1). https://doi.org/10.1101/cshperspect.a004978.

  7. Kadler, K. E., Holmes, D. F., Trotter, J. A., & Chapman, J. A. (1996). Collagen fibril formation. Biochemical Journal, 316(Pt 1), 1–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Hashmi, S., & Marinkovich, M. P. (2011). Molecular organization of the basement membrane zone. Clinics in Dermatology, 29(4), 398–411. https://doi.org/10.1016/j.clindermatol.2011.01.009.

    Article  PubMed  Google Scholar 

  9. Kadler, K. E., Baldock, C., Bella, J., & Boot-Handford, R. P. (2007). Collagens at a glance. Journal of Cell Science, 120(12), 1955–1958. https://doi.org/10.1242/jcs.03453.

    Article  PubMed  CAS  Google Scholar 

  10. Shoulders, M. D., & Raines, R. T. (2009). Collagen structure and stability. Annual Review of Biochemistry, 78, 929–958. https://doi.org/10.1146/annurev.biochem.77.032207.120833.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Bella, J., Eaton, M., Brodsky, B., & Berman, H. M. (1994). Crystal and molecular structure of a collagen-like peptide at 1.9 A resolution. Science (New York, N.Y.), 266(5182), 75–81. https://doi.org/10.1126/science.7695699.

    Article  CAS  Google Scholar 

  12. Persikov, A. V., Ramshaw, J. A. M., Kirkpatrick, A., & Brodsky, B. (2005). Electrostatic interactions involving lysine make major contributions to collagen triple-helix stability. Biochemistry, 44(5), 1414–1422. https://doi.org/10.1021/bi048216r.

  13. Nimni, M. E. (1983). Collagen: structure, function, and metabolism in normal and fibrotic tissues. Seminars in Arthritis and Rheumatism, 13(1), 1–86. https://doi.org/10.1016/0049-0172(83)90024-0.

    Article  PubMed  CAS  Google Scholar 

  14. Qi, Y., & Xu, R. (2018). Roles of PLODs in collagen synthesis and cancer progression. Frontiers in Cell and Development Biology, 6. https://doi.org/10.3389/fcell.2018.00066.

  15. Myllyharju, J. (2005). Intracellular post-translational modifications of collagens. In J. Brinckmann, H. Notbohm, & P. K. Müller (Eds.), Collagen (Vol. 247, pp. 115–147). Berlin, Heidelberg: Springer Berlin Heidelberg. https://doi.org/10.1007/b103821.

    Chapter  Google Scholar 

  16. Makareeva, E., & Leikin, S. (2007). Procollagen triple helix assembly: an unconventional chaperone-assisted folding paradigm. PLoS One, 2, 403–434. https://doi.org/10.1371/journal.pone.0001029.

    Article  CAS  Google Scholar 

  17. Martinek, N., Shahab, J., Sodek, J., & Ringuette, M. (2007). Is SPARC an evolutionarily conserved collagen chaperone? Journal of Dental Research, 86(4), 296–305. https://doi.org/10.1177/154405910708600402.

    Article  PubMed  CAS  Google Scholar 

  18. Giudici, C., Raynal, N., Wiedemann, H., Cabral, W. A., Marini, J. C., Timpl, R., et al. (2008). Map** of SPARC/BM-40/osteonectin-binding sites on fibrillar collagens. The Journal of Biological Chemistry, 283(28), 19551–19560. https://doi.org/10.1074/jbc.M710001200.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Morrissey, M. A., Jayadev, R., Miley, G. R., Blebea, C. A., Chi, Q., Ihara, S., & Sherwood, D. R. (2016). SPARC promotes cell invasion in vivo by decreasing type IV collagen levels in the basement membrane. PLoS Genetics, 12(2), e1005905. https://doi.org/10.1371/journal.pgen.1005905.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Karsdal, M. A. (2016). Introduction. In M. A. Karsdal (Ed.), Biochemistry of collagens, laminins and elastin (pp. xix–xxxiv). Academic Press. https://doi.org/10.1016/B978-0-12-809847-9.02001-8.

  21. Canty, E. G. (2005). Procollagen trafficking, processing and fibrillogenesis. Journal of Cell Science, 118(7), 1341–1353. https://doi.org/10.1242/jcs.01731.

    Article  PubMed  CAS  Google Scholar 

  22. Hopkins, D. R., Keles, S., & Greenspan, D. S. (2007). The bone morphogenetic protein 1/tolloid-like metalloproteinases. Matrix biology : journal of the International Society for Matrix Biology, 26(7), 508–523. https://doi.org/10.1016/j.matbio.2007.05.004.

    Article  CAS  Google Scholar 

  23. Imamura, Y., Steiglitz, B. M., & Greenspan, D. S. (1998). Bone morphogenetic protein-1 processes the NH2-terminal propeptide, and a furin-like proprotein convertase processes the COOH-terminal propeptide of pro-alpha1(V) collagen. The Journal of Biological Chemistry, 273(42), 27511–27517. https://doi.org/10.1074/jbc.273.42.27511.

    Article  PubMed  CAS  Google Scholar 

  24. Fukae, M., & Mechanic, G. L. (1980). Maturation of collagenous tissue. Temporal sequence of formation of peptidyl lysine-derived cross-linking aldehydes and cross-links in collagen. Journal of Biological Chemistry, 255(13), 6511–6518.

    PubMed  CAS  Google Scholar 

  25. Kuczek, D. E., Hübbe, M. L., & Madsen, D. H. (2017). Internalization of collagen: an important matrix turnover pathway in cancer. In R. A. Brekken & D. Stupack (Eds.), Extracellular matrix in tumor biology (pp. 17–38). Cham: Springer International Publishing. https://doi.org/10.1007/978-3-319-60907-2_2.

    Chapter  Google Scholar 

  26. Perumal, S., Antipova, O., & Orgel, J. P. R. O. (2008). Collagen fibril architecture, domain organization, and triple-helical conformation govern its proteolysis. Proceedings of the National Academy of Sciences, 105(8), 2824–2829. https://doi.org/10.1073/pnas.0710588105.

    Article  Google Scholar 

  27. Lee, M., Fridman, R., & Mobashery, S. (2004). Extracellular proteases as targets for treatment of cancer metastases. Chemical Society Reviews, 33(7), 401. https://doi.org/10.1039/b209224g.

    Article  PubMed  CAS  Google Scholar 

  28. DeClerck, Y. A. (2012). Desmoplasia: a response or a niche? Cancer Discovery, 2(9), 772–774. https://doi.org/10.1158/2159-8290.CD-12-0348.

    Article  PubMed  CAS  Google Scholar 

  29. Barsky, S. H., Green, W. R., Grotendorst, G. R., & Liotta, L. A. (1984). Desmoplastic breast carcinoma as a source of human myofibroblasts. The American Journal of Pathology, 115(3), 329–333.

    PubMed  PubMed Central  CAS  Google Scholar 

  30. Wolfe, J. N. (1976). Breast patterns as an index of risk for develo** breast cancer. AJR. American Journal of Roentgenology, 126(6), 1130–1137. https://doi.org/10.2214/ajr.126.6.1130.

    Article  PubMed  CAS  Google Scholar 

  31. Guo, Y. P., Martin, L. J., Hanna, W., Banerjee, D., Miller, N., Fishell, E., et al. (2001). Growth factors and stromal matrix proteins associated with mammographic densities. Cancer Epidemiology, Biomarkers & Prevention: A Publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 10(3), 243–248.

    CAS  Google Scholar 

  32. Boyd, N. F., Guo, H., Martin, L. J., Sun, L., Stone, J., Fishell, E., et al. (2007). Mammographic density and the risk and detection of breast cancer. New England Journal of Medicine, 356(3), 227–236. https://doi.org/10.1056/NEJMoa062790.

    Article  PubMed  CAS  Google Scholar 

  33. Ayala, G., Tuxhorn, J. A., Wheeler, T. M., Frolov, A., Scardino, P. T., Ohori, M., et al. (2003). Reactive stroma as a predictor of biochemical-free recurrence in prostate cancer. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 9(13), 4792–4801.

    CAS  Google Scholar 

  34. Provenzano, P. P., Cuevas, C., Chang, A. E., Goel, V. K., Von Hoff, D. D., & Hingorani, S. R. (2012). Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma. Cancer Cell, 21(3), 418–429. https://doi.org/10.1016/j.ccr.2012.01.007.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Shimosato, Y., Suzuki, A., Hashimoto, T., Nishiwaki, Y., Kodama, T., Yoneyama, T., & Kameya, T. (1980). Prognostic implications of fibrotic focus (scar) in small peripheral lung cancers. The American Journal of Surgical Pathology, 4(4), 365–373. https://doi.org/10.1097/00000478-198008000-00005.

    Article  PubMed  CAS  Google Scholar 

  36. Cardone, A., Tolino, A., Zarcone, R., Borruto Caracciolo, G., & Tartaglia, E. (1997). Prognostic value of desmoplastic reaction and lymphocytic infiltration in the management of breast cancer. Panminerva Medica, 39(3), 174–177.

    PubMed  CAS  Google Scholar 

  37. Hasebe, T., Sasaki, S., Imoto, S., Mukai, K., Yokose, T., & Ochiai, A. (2002). Prognostic significance of fibrotic focus in invasive ductal carcinoma of the breast: a prospective observational study. Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc, 15(5), 502–516. https://doi.org/10.1038/modpathol.3880555.

    Article  Google Scholar 

  38. Ueno, H., Jones, A. M., Wilkinson, K. H., Jass, J. R., & Talbot, I. C. (2004). Histological categorisation of fibrotic cancer stroma in advanced rectal cancer. Gut, 53(4), 581–586. https://doi.org/10.1136/gut.2003.028365.

  39. Ueno, H., Konishi, T., Ishikawa, Y., Shimazaki, H., Ueno, M., Aosasa, S., et al. (2014). Histologic categorization of fibrotic cancer stroma in the primary tumor is an independent prognostic index in resectable colorectal liver metastasis. The American Journal of Surgical Pathology, 38(10), 1380–1386. https://doi.org/10.1097/PAS.0000000000000232.

    Article  PubMed  Google Scholar 

  40. Bran. (2009). Keloids: current concepts of pathogenesis (Review). International Journal of Molecular Medicine, 24(3). https://doi.org/10.3892/ijmm_00000231.

  41. Ueno, H., Jones, A., Jass, J. R., & Talbot, I. C. (2002). Clinicopathological significance of the `keloid-like’ collagen and myxoid stroma in advanced rectal cancer. Histopathology, 40(4), 327–334. https://doi.org/10.1046/j.1365-2559.2002.01376.x.

    Article  PubMed  CAS  Google Scholar 

  42. Nearchou, I. P., Kajiwara, Y., Mochizuki, S., Harrison, D. J., Caie, P. D., & Ueno, H. (2019). Novel internationally verified method reports desmoplastic reaction as the most significant prognostic feature for disease-specific survival in stage II colorectal cancer. The American Journal of Surgical Pathology, 43(9), 1239. https://doi.org/10.1097/PAS.0000000000001304.

    Article  PubMed  Google Scholar 

  43. Shin, N., Son, G. M., Shin, D.-H., Kwon, M.-S., Park, B.-S., Kim, H.-S., et al. (2019). Cancer-associated fibroblasts and desmoplastic reactions related to cancer invasiveness in patients with colorectal cancer. Annals of Coloproctology, 35(1), 36–46. https://doi.org/10.3393/ac.2018.09.10.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Fujita, H., Ohuchida, K., Mizumoto, K., Nakata, K., Yu, J., Kayashima, T., et al. (2010). α-Smooth muscle actin expressing stroma promotes an aggressive tumor biology in pancreatic ductal adenocarcinoma. Pancreas, 39(8), 1254. https://doi.org/10.1097/MPA.0b013e3181dbf647.

    Article  PubMed  CAS  Google Scholar 

  45. Whatcott, C. J., Diep, C. H., Jiang, P., Watanabe, A., LoBello, J., Sima, C., et al. (2015). Desmoplasia in primary tumors and metastatic lesions of pancreatic cancer. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 21(15), 3561–3568. https://doi.org/10.1158/1078-0432.CCR-14-1051.

    Article  CAS  Google Scholar 

  46. Bever, K. M., Sugar, E. A., Bigelow, E., Sharma, R., Laheru, D., Wolfgang, C. L., et al. (2015). The prognostic value of stroma in pancreatic cancer in patients receiving adjuvant therapy. HPB, 17(4), 292–298. https://doi.org/10.1111/hpb.12334.

    Article  PubMed  Google Scholar 

  47. Wang, L. M., Silva, M. A., D’Costa, Z., Bockelmann, R., Soonawalla, Z., Liu, S., et al. (2016). The prognostic role of desmoplastic stroma in pancreatic ductal adenocarcinoma. Oncotarget, 7(4), 4183–4194. https://doi.org/10.18632/oncotarget.6770.

    Article  PubMed  Google Scholar 

  48. Willumsen, N., Ali, S. M., Leitzel, K., Drabick, J. J., Yee, N., Polimera, H. V., et al. (2019). Collagen fragments quantified in serum as measures of desmoplasia associate with survival outcome in patients with advanced pancreatic cancer. Scientific Reports, 9(1), 1–8. https://doi.org/10.1038/s41598-019-56268-3.

    Article  CAS  Google Scholar 

  49. Fang, M., Yuan, J., Peng, C., & Li, Y. (2014). Collagen as a double-edged sword in tumor progression. Tumour Biology, 35(4), 2871–2882. https://doi.org/10.1007/s13277-013-1511-7.

    Article  PubMed  CAS  Google Scholar 

  50. Perryman, L., & Erler, J. T. (2014). Lysyl oxidase in cancer research. Future Oncology (London, England), 10(9), 1709–1717. https://doi.org/10.2217/fon.14.39.

    Article  CAS  Google Scholar 

  51. Pankova, D., Chen, Y., Terajima, M., Schliekelman, M. J., Baird, B. N., Fahrenholtz, M., et al. (2016). Cancer-associated fibroblasts induce a collagen cross-link switch in tumor stroma. Molecular Cancer Research, 14(3), 287–295. https://doi.org/10.1158/1541-7786.MCR-15-0307.

    Article  PubMed  CAS  Google Scholar 

  52. Provenzano, P. P., Inman, D. R., Eliceiri, K. W., Trier, S. M., & Keely, P. J. (2008). Contact guidance mediated three-dimensional cell migration is regulated by Rho/ROCK-dependent matrix reorganization. Biophysical Journal, 95(11), 5374–5384. https://doi.org/10.1529/biophysj.108.133116.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Zhou, Z.-H., Ji, C.-D., **ao, H.-L., Zhao, H.-B., Cui, Y.-H., & Bian, X.-W. (2017). Reorganized collagen in the tumor microenvironment of gastric cancer and its association with prognosis. Journal of Cancer, 8(8), 1466–1476. https://doi.org/10.7150/jca.18466.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Bredfeldt, J. S., Liu, Y., Conklin, M. W., Keely, P. J., Mackie, T. R., & Eliceiri, K. W. (2014). Automated quantification of aligned collagen for human breast carcinoma prognosis. Journal of Pathology Informatics, 5(1), 28. https://doi.org/10.4103/2153-3539.139707.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Franchi, M., Masola, V., Bellin, G., Onisto, M., Karamanos, K.-A., & Piperigkou, Z. (2019). Collagen fiber array of peritumoral stroma influences epithelial-to-mesenchymal transition and invasive potential of mammary cancer cells. Journal of Clinical Medicine, 8(2). https://doi.org/10.3390/jcm8020213.

  56. Conklin, M. W., Eickhoff, J. C., Riching, K. M., Pehlke, C. A., Eliceiri, K. W., Provenzano, P. P., et al. (2011). Aligned collagen is a prognostic signature for survival in human breast carcinoma. The American Journal of Pathology, 178(3), 1221–1232. https://doi.org/10.1016/j.ajpath.2010.11.076.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Brabrand, A., Kariuki, I. I., Engstrøm, M. J., Haugen, O. A., Dyrnes, L. A., Åsvold, B. O., et al. (2015). Alterations in collagen fibre patterns in breast cancer. A premise for tumour invasiveness? APMIS, 123(1), 1–8. https://doi.org/10.1111/apm.12298.

    Article  PubMed  CAS  Google Scholar 

  58. Riching, K. M., Cox, B. L., Salick, M. R., Pehlke, C., Riching, A. S., Ponik, S. M., et al. (2014). 3D collagen alignment limits protrusions to enhance breast cancer cell persistence. Biophysical Journal, 107(11), 2546–2558. https://doi.org/10.1016/j.bpj.2014.10.035.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. Acerbi, I., Cassereau, L., Dean, I., Shi, Q., Au, A., Park, C., et al. (2015). Human breast cancer invasion and aggression correlates with ECM stiffening and immune cell infiltration. Integrative biology : quantitative biosciences from nano to macro, 7(10), 1120–1134. https://doi.org/10.1039/c5ib00040h.

    Article  CAS  Google Scholar 

  60. Naba, A., Clauser, K. R., Lamar, J. M., Carr, S. A., & Hynes, R. O. (2014). Extracellular matrix signatures of human mammary carcinoma identify novel metastasis promoters. eLife, 3, e01308. https://doi.org/10.7554/eLife.01308.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Zhang, H., Fredericks, T., **ong, G., Qi, Y., Rychahou, P. G., Li, J.-D., et al. (2018). Membrane associated collagen XIII promotes cancer metastasis and enhances anoikis resistance. Breast Cancer Research, 20(1), 116. https://doi.org/10.1186/s13058-018-1030-y.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  62. **ong, G., Deng, L., Zhu, J., Rychahou, P. G., & Xu, R. (2014). Prolyl-4-hydroxylase α subunit 2 promotes breast cancer progression and metastasis by regulating collagen deposition. BMC Cancer, 14, 1. https://doi.org/10.1186/1471-2407-14-1.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Damaghi, M., Byrne, S., Xu, L., Tafreshi, N., Fang, B., Koomen, J. M., … Gillies, R. J. (2019). Collagen production and niche engineering: a novel strategy for cancer cells to survive acidosis and evolve. bioRxiv, 711978. https://doi.org/10.1101/711978

  64. Pankova, D., Jiang, Y., Chatzifrangkeskou, M., Vendrell, I., Buzzelli, J., Ryan, A., … O’Neill, E. (2019). RASSF1A controls tissue stiffness and cancer stem-like cells in lung adenocarcinoma. The EMBO Journal, 38(13). 10.15252/embj.2018100532

  65. Fang, S., Dai, Y., Mei, Y., Yang, M., Hu, L., Yang, H., et al. (2019). Clinical significance and biological role of cancer-derived type I collagen in lung and esophageal cancers. Thoracic Cancer, 10(2), 277–288. https://doi.org/10.1111/1759-7714.12947.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Naba, A., Clauser, K. R., Hoersch, S., Liu, H., Carr, S. A., & Hynes, R. O. (2012). The matrisome: in silico definition and in vivo characterization by proteomics of normal and tumor extracellular matrices. Molecular & Cellular Proteomics : MCP, 11(4). https://doi.org/10.1074/mcp.M111.014647.

  67. Ohlund, D., Lundin, C., Ardnor, B., Oman, M., Naredi, P., & Sund, M. (2009). Type IV collagen is a tumour stroma-derived biomarker for pancreas cancer. British Journal of Cancer, 101(1), 91–97. https://doi.org/10.1038/sj.bjc.6605107.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  68. Ting, D. T., Wittner, B. S., Ligorio, M., Jordan, N. V., Shah, A. M., Miyamoto, D. T., et al. (2014). Single-cell RNA sequencing identifies extracellular matrix gene expression by pancreatic circulating tumor cells. Cell Reports, 8(6), 1905–1918. https://doi.org/10.1016/j.celrep.2014.08.029.

    Article  PubMed  CAS  Google Scholar 

  69. Miyake, M., Hori, S., Morizawa, Y., Tatsumi, Y., Toritsuka, M., Ohnishi, S., et al. (2017). Collagen type IV alpha 1 (COL4A1) and collagen type XIII alpha 1 (COL13A1) produced in cancer cells promote tumor budding at the invasion front in human urothelial carcinoma of the bladder. Oncotarget, 8(22), 36099–36114. https://doi.org/10.18632/oncotarget.16432.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Cavaco, A., Rezaei, M., Niland, S., & Eble, J. A. (2017). Collateral damage intended—cancer-associated fibroblasts and vasculature are potential targets in cancer therapy. International Journal of Molecular Sciences, 18(11), 2355. https://doi.org/10.3390/ijms18112355.

    Article  PubMed Central  CAS  Google Scholar 

  71. Liu, T., Zhou, L., Li, D., Andl, T., & Zhang, Y. (2019). Cancer-associated fibroblasts build and secure the tumor microenvironment. Frontiers in Cell and Developmental Biology, 7. https://doi.org/10.3389/fcell.2019.00060

  72. Hanley, C. J., Noble, F., Ward, M., Bullock, M., Drifka, C., Mellone, M., et al. (2015). A subset of myofibroblastic cancer-associated fibroblasts regulate collagen fiber elongation, which is prognostic in multiple cancers. Oncotarget, 7(5), 6159–6174. https://doi.org/10.18632/oncotarget.6740.

    Article  PubMed Central  Google Scholar 

  73. Faouzi, S., Le Bail, B., Neaud, V., Boussarie, L., Saric, J., Bioulac-Sage, P., et al. (1999). Myofibroblasts are responsible for collagen synthesis in the stroma of human hepatocellular carcinoma: an in vivo and in vitro study. Journal of Hepatology, 30(2), 275–284. https://doi.org/10.1016/s0168-8278(99)80074-9.

    Article  PubMed  CAS  Google Scholar 

  74. Kauppila, S., Stenbäck, F., Risteli, J., Jukkola, A., & Risteli, L. (1998). Aberrant type I and type III collagen gene expression in human breast cancer in vivo. The Journal of Pathology, 186(3), 262–268. https://doi.org/10.1002/(SICI)1096-9896(1998110)186:3<262::AID-PATH191>3.0.CO;2-3.

    Article  PubMed  CAS  Google Scholar 

  75. Bauer, M., Su, G., Casper, C., He, R., Rehrauer, W., & Friedl, A. (2010). Heterogeneity of gene expression in stromal fibroblasts of human breast carcinomas and normal breast. Oncogene, 29(12), 1732–1740. https://doi.org/10.1038/onc.2009.463.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  76. Bachem, M. G., Schneider, E., Groß, H., Weidenbach, H., Schmid, R. M., Menke, A., et al. (1998). Identification, culture, and characterization of pancreatic stellate cells in rats and humans. Gastroenterology, 115(2), 421–432. https://doi.org/10.1016/S0016-5085(98)70209-4.

    Article  PubMed  CAS  Google Scholar 

  77. Kwa, M. Q., Herum, K. M., & Brakebusch, C. (2019). Cancer-associated fibroblasts: how do they contribute to metastasis? Clinical & Experimental Metastasis, 36(2), 71–86. https://doi.org/10.1007/s10585-019-09959-0.

    Article  CAS  Google Scholar 

  78. Lambrechts, D., Wauters, E., Boeckx, B., Aibar, S., Nittner, D., Burton, O., et al. (2018). Phenotype molding of stromal cells in the lung tumor microenvironment. Nature Medicine, 24(8), 1277–1289. https://doi.org/10.1038/s41591-018-0096-5.

    Article  PubMed  CAS  Google Scholar 

  79. Lai, S. L., Tan, M. L., Hollows, R. J., Robinson, M., Ibrahim, M., Margielewska, S., et al. (2019). Collagen induces a more proliferative, migratory and chemoresistant phenotype in head and neck cancer via DDR1. Cancers, 11(11). https://doi.org/10.3390/cancers11111766.

  80. Karagiannis, G. S., Petraki, C., Prassas, I., Saraon, P., Musrap, N., Dimitromanolakis, A., & Diamandis, E. P. (2012). Proteomic signatures of the desmoplastic invasion front reveal collagen type XII as a marker of myofibroblastic differentiation during colorectal cancer metastasis. Oncotarget, 3(3), 267–285.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Väisänen, T., Väisänen, M.-R., Autio-Harmainen, H., & Pihlajaniemi, T. (2005). Type XIII collagen expression is induced during malignant transformation in various epithelial and mesenchymal tumours. The Journal of Pathology, 207(3), 324–335. https://doi.org/10.1002/path.1836.

    Article  PubMed  CAS  Google Scholar 

  82. Karousou, E., D’Angelo, M. L., Kouvidi, K., Vigetti, D., Viola, M., Nikitovic, D., … Passi, A. (2014). Collagen VI and hyaluronan: the common role in breast cancer. BioMed Research International. Research article. https://doi.org/10.1155/2014/606458

  83. Schnoor, M., Cullen, P., Lorkowski, J., Stolle, K., Robenek, H., Troyer, D., et al. (2008). Production of type VI collagen by human macrophages: a new dimension in macrophage functional heterogeneity. Journal of Immunology (Baltimore, Md.: 1950), 180(8), 5707–5719. https://doi.org/10.4049/jimmunol.180.8.5707.

    Article  CAS  Google Scholar 

  84. Varol, C., & Sagi, I. (2018). Phagocyte—extracellular matrix crosstalk empowers tumor development and dissemination. The FEBS Journal, 285(4), 734–751. https://doi.org/10.1111/febs.14317.

    Article  PubMed  CAS  Google Scholar 

  85. Afik, R., Zigmond, E., Vugman, M., Klepfish, M., Shimshoni, E., Pasmanik-Chor, M., et al. (2016). Tumor macrophages are pivotal constructors of tumor collagenous matrix. The Journal of Experimental Medicine, 213(11), 2315–2331. https://doi.org/10.1084/jem.20151193.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  86. Ingman, W. V., Wyckoff, J., Gouon-Evans, V., Condeelis, J., & Pollard, J. W. (2006). Macrophages promote collagen fibrillogenesis around terminal end buds of the develo** mammary gland. Developmental Dynamics: An Official Publication of the American Association of the Anatomists, 235(12), 3222–3229. https://doi.org/10.1002/dvdy.20972.

    Article  CAS  Google Scholar 

  87. Casimiro, S., Ferreira, A. R., Mansinho, A., Alho, I., & Costa, L. (2016). Molecular mechanisms of bone metastasis: which targets came from the bench to the bedside? International Journal of Molecular Sciences, 17(9). https://doi.org/10.3390/ijms17091415.

  88. Condeelis, J., & Segall, J. E. (2003). Intravital imaging of cell movement in tumours. Nature Reviews Cancer, 3(12), 921–930. https://doi.org/10.1038/nrc1231.

  89. Qiu, S., Deng, L., Liao, X., Nie, L., Qi, F., **, K., et al. (2019). Tumor-associated macrophages promote bladder tumor growth through PI3K/AKT signal induced by collagen. Cancer Science, 110(7), 2110–2118. https://doi.org/10.1111/cas.14078.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  90. Wei, X., Li, S., He, J., Du, H., Liu, Y., Yu, W., et al. (2019). Tumor-secreted PAI-1 promotes breast cancer metastasis via the induction of adipocyte-derived collagen remodeling. Cell Communication and Signaling: CCS, 17(1), 58. https://doi.org/10.1186/s12964-019-0373-z.

    Article  CAS  PubMed Central  Google Scholar 

  91. Iyengar, P., Espina, V., Williams, T. W., Lin, Y., Berry, D., Jelicks, L. A., et al. (2005). Adipocyte-derived collagen VI affects early mammary tumor progression in vivo, demonstrating a critical interaction in the tumor/stroma microenvironment. Journal of Clinical Investigation, 115(5), 1163–1176. https://doi.org/10.1172/JCI200523424.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  92. Weilbaecher, K. N., Guise, T. A., & McCauley, L. K. (2011). Cancer to bone: a fatal attraction. Nature Reviews. Cancer, 11(6), 411–425. https://doi.org/10.1038/nrc3055

  93. Kolb, A. D., & Bussard, K. M. (2019). The bone extracellular matrix as an ideal milieu for cancer cell metastases. Cancers, 11(7). https://doi.org/10.3390/cancers11071020.

  94. Januchowski, R., Zawierucha, P., Ruciński, M., Nowicki, M., & Zabel, M. (2014). Extracellular matrix proteins expression profiling in chemoresistant variants of the A2780 ovarian cancer cell line. BioMed Research International, 2014, 365867. https://doi.org/10.1155/2014/365867.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  95. Kanematsu, A., Marui, A., Yamamoto, S., Ozeki, M., Hirano, Y., Yamamoto, M., et al. (2004). Type I collagen can function as a reservoir of basic fibroblast growth factor. Journal of Controlled Release, 99(2), 281–292. https://doi.org/10.1016/j.jconrel.2004.07.008.

    Article  PubMed  CAS  Google Scholar 

  96. Jain, R. K. (2003). Molecular regulation of vessel maturation. Nature Medicine, 9(6), 685–693. https://doi.org/10.1038/nm0603-685.

    Article  PubMed  CAS  Google Scholar 

  97. Seandel, M., Noack-Kunnmann, K., Zhu, D., Aimes, R. T., & Quigley, J. P. (2001). Growth factor-induced angiogenesis in vivo requires specific cleavage of fibrillar type I collagen. Blood, 97(8), 2323–2332. https://doi.org/10.1182/blood.v97.8.2323.

  98. Menke, A., Philippi, C., Vogelmann, R., Seidel, B., Lutz, M. P., Adler, G., & Wedlich, D. (2001). Down-regulation of E-cadherin gene expression by collagen type I and type III in pancreatic cancer cell lines. Cancer Research, 61(8), 3508–3517.

    PubMed  CAS  Google Scholar 

  99. Shields, M. A., Dangi-Garimella, S., Krantz, S. B., Bentrem, D. J., & Munshi, H. G. (2011). Pancreatic cancer cells respond to type I collagen by inducing snail expression to promote membrane type 1 matrix metalloproteinase-dependent collagen invasion. The Journal of Biological Chemistry, 286(12), 10495–10504. https://doi.org/10.1074/jbc.M110.195628.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  100. Jang, M., Koh, I., Lee, J. E., Lim, J. Y., Cheong, J.-H., & Kim, P. (2018). Increased extracellular matrix density disrupts E-cadherin/β-catenin complex in gastric cancer cells. Biomaterials Science, 6(10), 2704–2713. https://doi.org/10.1039/C8BM00843D.

    Article  PubMed  CAS  Google Scholar 

  101. Di Martino, J., Moreau, V., & Saltel, F. (2015). Type I collagen fibrils: an inducer of invadosomes. Oncotarget, 6(30), 28519–28520.

    Article  PubMed  PubMed Central  Google Scholar 

  102. Juin, A., Billottet, C., Moreau, V., Destaing, O., Albiges-Rizo, C., Rosenbaum, J., et al. (2012). Physiological type I collagen organization induces the formation of a novel class of linear invadosomes. Molecular Biology of the Cell, 23(2), 297–309. https://doi.org/10.1091/mbc.E11-07-0594.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  103. Juin, A., Di Martino, J., Leitinger, B., Henriet, E., Gary, A.-S., Paysan, L., et al. (2014). Discoidin domain receptor 1 controls linear invadosome formation via a Cdc42-Tuba pathway. The Journal of Cell Biology, 207(4), 517–533. https://doi.org/10.1083/jcb.201404079.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  104. Gao, H., Chakraborty, G., Zhang, Z., Akalay, I., Gadiya, M., Gao, Y., et al. (2016). Multi-organ site metastatic reactivation mediated by non-canonical discoidin domain receptor 1 signaling. Cell, 166(1), 47–62. https://doi.org/10.1016/j.cell.2016.06.009.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  105. Barcus, C. E., O’Leary, K. A., Brockman, J. L., Rugowski, D. E., Liu, Y., Garcia, N., et al. (2017). Elevated collagen-I augments tumor progressive signals, intravasation and metastasis of prolactin-induced estrogen receptor alpha positive mammary tumor cells. Breast cancer research: BCR, 19(1), 9. https://doi.org/10.1186/s13058-017-0801-1.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  106. Hall, C. L., Dai, J., van Golen, K. L., Keller, E. T., & Long, M. W. (2006). Type I collagen receptor (alpha 2 beta 1) signaling promotes the growth of human prostate cancer cells within the bone. Cancer Research, 66(17), 8648–8654. https://doi.org/10.1158/0008-5472.CAN-06-1544.

    Article  PubMed  CAS  Google Scholar 

  107. Clarke, C. J., Berg, T. J., Birch, J., Ennis, D., Mitchell, L., Cloix, C., et al. (2016). The initiator methionine tRNA drives secretion of type II collagen from stromal fibroblasts to promote tumor growth and angiogenesis. Current Biology, 26(6), 755–765. https://doi.org/10.1016/j.cub.2016.01.045.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  108. Chintala, S. K., Sawaya, R., Gokaslan, Z. L., & Rao, J. S. (1996). The effect of type III collagen on migration and invasion of human glioblastoma cell lines in vitro. Cancer Letters, 102(1–2), 57–63. https://doi.org/10.1016/0304-3835(96)04163-8.

    Article  PubMed  CAS  Google Scholar 

  109. Wang, Z.-N., & Xu, H.-M. (2000). Relationship between collagen IV expression and biological behavior of gastric cancer. World Journal of Gastroenterology, 6(3), 438–439. https://doi.org/10.3748/wjg.v6.i3.438.

    Article  PubMed  PubMed Central  Google Scholar 

  110. Öhlund, D., Franklin, O., Lundberg, E., Lundin, C., & Sund, M. (2013). Type IV collagen stimulates pancreatic cancer cell proliferation, migration, and inhibits apoptosis through an autocrine loop. BMC Cancer, 13, 154. https://doi.org/10.1186/1471-2407-13-154.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  111. Aznavoorian, S., Stracke, M. L., Krutzsch, H., Schiffmann, E., & Liotta, L. A. (1990). Signal transduction for chemotaxis and haptotaxis by matrix molecules in tumor cells. The Journal of Cell Biology, 110(4), 1427–1438. https://doi.org/10.1083/jcb.110.4.1427.

    Article  PubMed  CAS  Google Scholar 

  112. Barsky, S. H., Rao, C. N., Grotendorst, G. R., & Liotta, L. A. (1982). Increased content of type V collagen in desmoplasia of human breast carcinoma. The American Journal of Pathology, 108(3), 276–283.

    PubMed  PubMed Central  CAS  Google Scholar 

  113. Huang, G., Ge, G., Izzi, V., & Greenspan, D. S. (2017). α3 Chains of type V collagen regulate breast tumour growth via glypican-1. Nature Communications, 8. https://doi.org/10.1038/ncomms14351.

  114. Berchtold, S., Grünwald, B., Krüger, A., Reithmeier, A., Hähl, T., Cheng, T., et al. (2015). Collagen type V promotes the malignant phenotype of pancreatic ductal adenocarcinoma. Cancer Letters, 356(2 Pt B), 721–732. https://doi.org/10.1016/j.canlet.2014.10.020.

    Article  PubMed  CAS  Google Scholar 

  115. Wright, A., Li, Y.-H., & Zhu, C. (2008). The differential effect of endothelial cell factors on in vitro motility of malignant and non-malignant cells. Annals of Biomedical Engineering, 36(6), 958–969. https://doi.org/10.1007/s10439-008-9489-9.

    Article  PubMed  PubMed Central  Google Scholar 

  116. Huang, Y., Li, G., Wang, K., Mu, Z., **e, Q., Qu, H., et al. (2018). Collagen type VI alpha 3 chain promotes epithelial-mesenchymal transition in bladder cancer cells via transforming growth factor β (TGF-β)/Smad pathway. Medical Science Monitor : International Medical Journal of Experimental and Clinical Research, 24, 5346–5354. https://doi.org/10.12659/MSM.909811.

    Article  CAS  Google Scholar 

  117. Owusu-Ansah, K. G., Song, G., Chen, R., Edoo, M. I. A., Li, J., Chen, B., et al. (2019). COL6A1 promotes metastasis and predicts poor prognosis in patients with pancreatic cancer. International Journal of Oncology, 55(2), 391–404. https://doi.org/10.3892/ijo.2019.4825.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  118. You, W.-K., Bonaldo, P., & Stallcup, W. B. (2012). Collagen VI ablation retards brain tumor progression due to deficits in assembly of the vascular basal lamina. The American Journal of Pathology, 180(3), 1145–1158. https://doi.org/10.1016/j.ajpath.2011.11.006.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  119. Martins, V. L., Caley, M. P., Moore, K., Szentpetery, Z., Marsh, S. T., Murrell, D. F., et al. (2016). Suppression of TGFβ and angiogenesis by type VII collagen in cutaneous SCC. Journal of the National Cancer Institute, 108(1). https://doi.org/10.1093/jnci/djv293.

  120. Oktem, G., Sercan, O., Guven, U., Uslu, R., Uysal, A., Goksel, G., et al. (2014). Cancer stem cell differentiation: TGFβ1 and versican may trigger molecules for the organization of tumor spheroids. Oncology Reports, 32(2), 641–649. https://doi.org/10.3892/or.2014.3252.

    Article  PubMed  CAS  Google Scholar 

  121. Zhao, Y., Jia, L., Mao, X., Xu, H., Wang, B., & Liu, Y. (2009). siRNA-targeted COL8A1 inhibits proliferation, reduces invasion and enhances sensitivity to D-limonence treatment in hepatocarcinoma cells. IUBMB Life, 61(1), 74–79. https://doi.org/10.1002/iub.151.

    Article  PubMed  CAS  Google Scholar 

  122. ang, W., Xu, G., Ding, C.-L., Zhao, L.-J., Zhao, P., Ren, H., & Qi, Z.-T. (2013). All-trans retinoic acid protects hepatocellular carcinoma cells against serum-starvation-induced cell death by upregulating collagen 8A2. The FEBS Journal, 280(5), 1308–1319. https://doi.org/10.1111/febs.12122.

    Article  CAS  Google Scholar 

  123. Chapman, K. B., Prendes, M. J., Sternberg, H., Kidd, J. L., Funk, W. D., Wagner, J., & West, M. D. (2012). COL10A1 expression is elevated in diverse solid tumor types and is associated with tumor vasculature. Future Oncology (London, England), 8(8), 1031–1040. https://doi.org/10.2217/fon.12.79.

    Article  CAS  Google Scholar 

  124. Huang, H., Li, T., Ye, G., Zhao, L., Zhang, Z., Mo, D., et al. (2018). High expression of COL10A1 is associated with poor prognosis in colorectal cancer. OncoTargets and Therapy, 11, 1571–1581. https://doi.org/10.2147/OTT.S160196.

    Article  PubMed  PubMed Central  Google Scholar 

  125. van Huizen, N. A., Coebergh van den Braak, R. R. J., Doukas, M., Dekker, L. J. M., IJzermans, J. N. M., & Luider, T. M. (2019). Up-regulation of collagen proteins in colorectal liver metastasis compared with normal liver tissue. The Journal of Biological Chemistry, 294(1), 281–289. https://doi.org/10.1074/jbc.RA118.005087.

    Article  PubMed  Google Scholar 

  126. Fischer, H., Stenling, R., Rubio, C., & Lindblom, A. (2001). Colorectal carcinogenesis is associated with stromal expression of COL11A1 and COL5A2. Carcinogenesis, 22(6), 875–878. https://doi.org/10.1093/carcin/22.6.875.

    Article  PubMed  CAS  Google Scholar 

  127. Shen, L., Yang, M., Lin, Q., Zhang, Z., Zhu, B., & Miao, C. (2016). COL11A1 is overexpressed in recurrent non-small cell lung cancer and promotes cell proliferation, migration, invasion and drug resistance. Oncology Reports, 36(2), 877–885. https://doi.org/10.3892/or.2016.4869.

    Article  PubMed  CAS  Google Scholar 

  128. Zhao, Y., Zhou, T., Li, A., Yao, H., He, F., Wang, L., & Si, J. (2009). A potential role of collagens expression in distinguishing between premalignant and malignant lesions in stomach. Anatomical Record (Hoboken, N.J.: 2007), 292(5), 692–700. https://doi.org/10.1002/ar.20874.

    Article  CAS  Google Scholar 

  129. García-Pravia, C., Galván, J. A., Gutiérrez-Corral, N., Solar-García, L., García-Pérez, E., García-Ocaña, M., et al. (2013). Overexpression of COL11A1 by cancer-associated fibroblasts: clinical relevance of a stromal marker in pancreatic cancer. PLoS One, 8(10), e78327. https://doi.org/10.1371/journal.pone.0078327.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  130. Feng, Y., Sun, B., Li, X., Zhang, L., Niu, Y., **ao, C., et al. (2007). Differentially expressed genes between primary cancer and paired lymph node metastases predict clinical outcome of node-positive breast cancer patients. Breast Cancer Research and Treatment, 103(3), 319–329. https://doi.org/10.1007/s10549-006-9385-7.

    Article  PubMed  CAS  Google Scholar 

  131. Sok, J. C., Lee, J. A., Dasari, S., Joyce, S., Contrucci, S. C., Egloff, A. M., et al. (2013). Collagen type XI α1 facilitates head and neck squamous cell cancer growth and invasion. British Journal of Cancer, 109(12), 3049–3056. https://doi.org/10.1038/bjc.2013.624.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  132. Yen, T.-Y., Haste, N., Timpe, L. C., Litsakos-Cheung, C., Yen, R., & Macher, B. A. (2014). Using a cell line breast cancer progression system to identify biomarker candidates. Journal of Proteomics, 96, 173–183. https://doi.org/10.1016/j.jprot.2013.11.006.

    Article  PubMed  CAS  Google Scholar 

  133. Reddy, L. A., Mikesh, L., Moskulak, C., Harvey, J., Sherman, N., Zigrino, P., et al. (2014). Host response to human breast invasive ductal carcinoma (IDC) as observed by changes in the stromal proteome. Journal of Proteome Research, 13(11), 4739–4751. https://doi.org/10.1021/pr500620x.

    Article  PubMed  CAS  Google Scholar 

  134. Verghese, E. T., Drury, R., Green, C. A., Holliday, D. L., Lu, X., Nash, C., et al. (2013). MiR-26b is down-regulated in carcinoma-associated fibroblasts from ER-positive breast cancers leading to enhanced cell migration and invasion. The Journal of Pathology, 231(3), 388–399. https://doi.org/10.1002/path.4248.

    Article  PubMed  CAS  Google Scholar 

  135. Karagiannis, G. S., Petraki, C., Prassas, I., Saraon, P., Musrap, N., Dimitromanolakis, A., & Diamandis, E. P. (2012). Proteomic signatures of the desmoplastic invasion front reveal collagen type XII as a marker of myofibroblastic differentiation during colorectal cancer metastasis. Oncotarget, 3(3), 267–285. https://doi.org/10.18632/oncotarget.451.

    Article  PubMed  PubMed Central  Google Scholar 

  136. Hurskainen, M., Ruggiero, F., Hägg, P., Pihlajaniemi, T., & Huhtala, P. (2010). Recombinant human collagen XV regulates cell adhesion and migration. The Journal of Biological Chemistry, 285(8), 5258–5265. https://doi.org/10.1074/jbc.M109.033787.

    Article  PubMed  CAS  Google Scholar 

  137. Clementz, A. G., & Harris, A. (2013). Collagen XV: exploring its structure and its role within the tumor microenvironment. Molecular cancer research : MCR, 11(12), 1481–1486. https://doi.org/10.1158/1541-7786.MCR-12-0662.

    Article  PubMed  CAS  Google Scholar 

  138. Bauer, R., Ratzinger, S., Wales, L., Bosserhoff, A., Senner, V., Grifka, J., & Grässel, S. (2011). Inhibition of collagen XVI expression reduces glioma cell invasiveness. Cellular Physiology and Biochemistry: International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, 27(3–4), 217–226. https://doi.org/10.1159/000327947.

    Article  CAS  Google Scholar 

  139. Ratzinger, S., Grässel, S., Dowejko, A., Reichert, T. E., & Bauer, R. J. (2011). Induction of type XVI collagen expression facilitates proliferation of oral cancer cells. Matrix Biology: Journal of the International Society for Matrix Biology, 30(2), 118–125. https://doi.org/10.1016/j.matbio.2011.01.001.

    Article  CAS  Google Scholar 

  140. Maegdefrau, U., & Bosserhoff, A.-K. (2012). BMP activated Smad signaling strongly promotes migration and invasion of hepatocellular carcinoma cells. Experimental and Molecular Pathology, 92(1), 74–81. https://doi.org/10.1016/j.yexmp.2011.10.004.

    Article  PubMed  CAS  Google Scholar 

  141. Banyard, J., Bao, L., Hofer, M. D., Zurakowski, D., Spivey, K. A., Feldman, A. S., et al. (2007). Collagen XXIII expression is associated with prostate cancer recurrence and distant metastases. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 13(9), 2634–2642. https://doi.org/10.1158/1078-0432.CCR-06-2163.

    Article  CAS  Google Scholar 

  142. Spivey, K. A., Chung, I., Banyard, J., Adini, I., Feldman, H. A., & Zetter, B. R. (2012). A role for collagen XXIII in cancer cell adhesion, anchorage-independence, and metastasis. Oncogene, 31(18), 2362–2372. https://doi.org/10.1038/onc.2011.406.

    Article  PubMed  CAS  Google Scholar 

  143. Najafi, M., Farhood, B., & Mortezaee, K. (2019). Extracellular matrix (ECM) stiffness and degradation as cancer drivers. Journal of Cellular Biochemistry, 120(3), 2782–2790. https://doi.org/10.1002/jcb.27681.

    Article  PubMed  CAS  Google Scholar 

  144. Monboisse, J. C., Oudart, J. B., Ramont, L., Brassart-Pasco, S., & Maquart, F. X. (2014). Matrikines from basement membrane collagens: a new anti-cancer strategy. Biochimica et Biophysica Acta, 1840(8), 2589–2598. https://doi.org/10.1016/j.bbagen.2013.12.029.

    Article  PubMed  CAS  Google Scholar 

  145. Palmieri, D., Camardella, L., Ulivi, V., Guasco, G., & Manduca, P. (2000). Trimer carboxyl propeptide of collagen I produced by mature osteoblasts is chemotactic for endothelial cells. The Journal of Biological Chemistry, 275(42), 32658–32663. https://doi.org/10.1074/jbc.M002698200.

    Article  PubMed  CAS  Google Scholar 

  146. Palmieri, D., Astigiano, S., Barbieri, O., Ferrari, N., Marchisio, S., Ulivi, V., et al. (2008). Procollagen I COOH-terminal fragment induces VEGF-A and CXCR4 expression in breast carcinoma cells. Experimental Cell Research, 314(11), 2289–2298. https://doi.org/10.1016/j.yexcr.2008.04.016.

    Article  PubMed  CAS  Google Scholar 

  147. Visigalli, D., Palmieri, D., Strangio, A., Astigiano, S., Barbieri, O., Casartelli, G., et al. (2009). The carboxyl terminal trimer of procollagen I induces pro-metastatic changes and vascularization in breast cancer cells xenografts. BMC Cancer, 9, 59. https://doi.org/10.1186/1471-2407-9-59.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  148. Hayashi, S., Wang, Z., Bryan, J., Kobayashi, C., Faccio, R., & Sandell, L. J. (2011). The type II collagen N-propeptide, PIIBNP, inhibits cell survival and bone resorption of osteoclasts via integrin-mediated signaling. Bone, 49(4), 644–652. https://doi.org/10.1016/j.bone.2011.06.011.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  149. Wang, Z., Bryan, J., Franz, C., Havlioglu, N., & Sandell, L. J. (2010). Type IIB procollagen NH(2)-propeptide induces death of tumor cells via interaction with integrins alpha(V)beta(3) and alpha(V)beta(5). The Journal of Biological Chemistry, 285(27), 20806–20817. https://doi.org/10.1074/jbc.M110.118521.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  150. Sandell, L. J., Wang, Z., Franz, C., Bryan, J., Siegel, A., Mecham, R., et al. (2008). Live-cell imaging of endothelial cell tube formation: inhibition by chondrostatin. The FASEB Journal, 22(1_supplement), 101.4–101.4. https://doi.org/10.1096/fasebj.22.1_supplement.101.4.

    Article  Google Scholar 

  151. Wang, Z., Bryan, J., Franz, C., Siegel, A., Wagenseil, J., Mecham, R., & Sandell, L. J. (2008). A fragment of cartilage collagen, chondrostatin, inhibits migration of breast cancer cells. The FASEB Journal, 22(1_supplement), 1029.11–1029.11. https://doi.org/10.1096/fasebj.22.1_supplement.1029.11.

    Article  Google Scholar 

  152. Ghajar, C. M., George, S. C., & Putnam, A. J. (2008). Matrix metalloproteinase control of capillary morphogenesis. Critical Reviews in Eukaryotic Gene Expression, 18(3), 251–278.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Lv, Y., & Zheng, J. (2012). The inhibitory effects of Arresten protein on tumor formation. Chinese Medical Sciences Journal, 27(1), 11–17. https://doi.org/10.1016/S1001-9294(12)60016-9.

    Article  PubMed  CAS  Google Scholar 

  154. Aikio, M., Alahuhta, I., Nurmenniemi, S., Suojanen, J., Palovuori, R., Teppo, S., et al. (2012). Arresten, a collagen-derived angiogenesis inhibitor, suppresses invasion of squamous cell carcinoma. PLoS One, 7(12). https://doi.org/10.1371/journal.pone.0051044.

  155. Okada, M., & Yamawaki, H. (2019). A current perspective of canstatin, a fragment of type IV collagen alpha 2 chain. Journal of Pharmacological Sciences, 139(2), 59–64. https://doi.org/10.1016/j.jphs.2018.12.001.

    Article  PubMed  CAS  Google Scholar 

  156. Kamphaus, G. D., Colorado, P. C., Panka, D. J., Hopfer, H., Ramchandran, R., Torre, A., et al. (2000). Canstatin, a novel matrix-derived inhibitor of angiogenesis and tumor growth. The Journal of Biological Chemistry, 275(2), 1209–1215. https://doi.org/10.1074/jbc.275.2.1209.

    Article  PubMed  CAS  Google Scholar 

  157. He, G.-A., Luo, J.-X., Zhang, T.-Y., Wang, F.-Y., & Li, R.-F. (2003). Canstatin-N fragment inhibits in vitro endothelial cell proliferation and suppresses in vivo tumor growth. Biochemical and Biophysical Research Communications, 312(3), 801–805. https://doi.org/10.1016/j.bbrc.2003.11.003.

    Article  PubMed  CAS  Google Scholar 

  158. Maeshima, Y., Manfredi, M., Reimer, C., Holthaus, K. A., Hopfer, H., Chandamuri, B. R., et al. (2001). Identification of the anti-angiogenic site within vascular basement membrane-derived tumstatin. The Journal of Biological Chemistry, 276(18), 15240–15248. https://doi.org/10.1074/jbc.M007764200.

    Article  PubMed  CAS  Google Scholar 

  159. Sudhakar, A., Sugimoto, H., Yang, C., Lively, J., Zeisberg, M., & Kalluri, R. (2003). Human tumstatin and human endostatin exhibit distinct antiangiogenic activities mediated by alpha v beta 3 and alpha 5 beta 1 integrins. Proceedings of the National Academy of Sciences of the United States of America, 100(8), 4766–4771. https://doi.org/10.1073/pnas.0730882100.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  160. Mott, J. D., & Werb, Z. (2004). Regulation of matrix biology by matrix metalloproteinases. Current Opinion in Cell Biology, 16(5), 558–564. https://doi.org/10.1016/j.ceb.2004.07.010.

  161. Brassart-Pasco, S., Sénéchal, K., Thevenard, J., Ramont, L., Devy, J., Stefano, L. D., et al. (2012). Tetrastatin, the NC1 domain of the α4(IV) collagen chain: a novel potent anti-tumor matrikine. PLoS One, 7(4), e29587. https://doi.org/10.1371/journal.pone.0029587.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  162. Lambert, E., Fuselier, E., Ramont, L., Brassart, B., Dukic, S., Oudart, J.-B., et al. (2018). Conformation-dependent binding of a Tetrastatin peptide to α v β 3 integrin decreases melanoma progression through FAK/PI 3 K/Akt pathway inhibition. Scientific Reports, 8(1), 1–13. https://doi.org/10.1038/s41598-018-28003-x.

    Article  CAS  Google Scholar 

  163. Karagiannis, E. D., & Popel, A. S. (2007). Identification of novel short peptides derived from the α4, α5, and α6 fibrils of type IV collagen with anti-angiogenic properties. Biochemical and Biophysical Research Communications, 354(2), 434–439. https://doi.org/10.1016/j.bbrc.2006.12.231.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  164. Koskimaki, J. E., Karagiannis, E. D., Tang, B. C., Hammers, H., Watkins, D. N., Pili, R., & Popel, A. S. (2010). Pentastatin-1, a collagen IV derived 20-mer peptide, suppresses tumor growth in a small cell lung cancer xenograft model. BMC Cancer, 10(1), 29. https://doi.org/10.1186/1471-2407-10-29.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  165. Motrescu, E. R., Blaise, S., Etique, N., Messaddeq, N., Chenard, M.-P., Stoll, I., et al. (2008). Matrix metalloproteinase-11/stromelysin-3 exhibits collagenolytic function against collagen VI under normal and malignant conditions. Oncogene, 27(49), 6347–6355. https://doi.org/10.1038/onc.2008.218.

    Article  PubMed  CAS  Google Scholar 

  166. Park, J., & Scherer, P. E. (2012). Adipocyte-derived endotrophin promotes malignant tumor progression. The Journal of Clinical Investigation, 122(11), 4243–4256. https://doi.org/10.1172/JCI63930.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  167. Ortiz-Urda, S., Garcia, J., Green, C. L., Chen, L., Lin, Q., Veitch, D. P., et al. (2005). Type VII collagen is required for Ras-driven human epidermal tumorigenesis. Science (New York, N.Y.), 307(5716), 1773–1776. https://doi.org/10.1126/science.1106209.

    Article  CAS  Google Scholar 

  168. Xu, R., Yao, Z.-Y., **n, L., Zhang, Q., Li, T.-P., & Gan, R.-B. (2001). NC1 domain of human type VIII collagen (α 1) inhibits bovine aortic endothelial cell proliferation and causes cell apoptosis. Biochemical and Biophysical Research Communications, 289(1), 264–268. https://doi.org/10.1006/bbrc.2001.5970.

    Article  PubMed  CAS  Google Scholar 

  169. Shen, Z., Yao, C., Wang, Z., Yue, L., Fang, Z., Yao, H., et al. (2016). Vastatin, an endogenous antiangiogenesis polypeptide that is lost in hepatocellular carcinoma, effectively inhibits tumor metastasis. Molecular Therapy, 24(8), 1358–1368. https://doi.org/10.1038/mt.2016.56.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  170. Li, Y., Li, J., Woo, Y. M., Shen, Z., Yao, H., Cai, Y., et al. (2017). Enhanced expression of Vastatin inhibits angiogenesis and prolongs survival in murine orthotopic glioblastoma model. BMC Cancer, 17(1), 126. https://doi.org/10.1186/s12885-017-3125-8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  171. Willumsen, N., Jorgensen, L. N., & Karsdal, M. A. (2019). Vastatin (the NC1 domain of human type VIII collagen a1 chain) is linked to stromal reactivity and elevated in serum from patients with colorectal cancer. Cancer Biology & Therapy, 20(5), 692–699. https://doi.org/10.1080/15384047.2018.1550571.

    Article  CAS  Google Scholar 

  172. Ramchandran, R., Dhanabal, M., Volk, R., Waterman, M. J. F., Segal, M., Lu, H., et al. (1999). Antiangiogenic activity of Restin, NC10 domain of human collagen XV: comparison to endostatin. Biochemical and Biophysical Research Communications, 255(3), 735–739. https://doi.org/10.1006/bbrc.1999.0248.

    Article  PubMed  CAS  Google Scholar 

  173. Mutolo, M. J., Morris, K. J., Leir, S.-H., Caffrey, T. C., Lewandowska, M. A., Hollingsworth, M. A., & Harris, A. (2012). Tumor suppression by collagen XV is independent of the restin domain. Matrix Biology, 31(5), 285–289. https://doi.org/10.1016/j.matbio.2012.03.003.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  174. O’Reilly, M. S., Boehm, T., Shing, Y., Fukai, N., Vasios, G., Lane, W. S., et al. (1997). Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell, 88(2), 277–285. https://doi.org/10.1016/S0092-8674(00)81848-6.

    Article  PubMed  Google Scholar 

  175. Boehm, T., Folkman, J., Browder, T., & O’Reilly, M. S. (1997). Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance. Nature, 390(6658), 404–407. https://doi.org/10.1038/37126.

    Article  PubMed  CAS  Google Scholar 

  176. Felbor, U., Dreier, L., Bryant, R. A. R., Ploegh, H. L., Olsen, B. R., & Mothes, W. (2000). Secreted cathepsin L generates endostatin from collagen XVIII. The EMBO Journal, 19(6), 1187–1194. https://doi.org/10.1093/emboj/19.6.1187.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  177. Kim, Y.-M., Hwang, S., Kim, Y.-M., Pyun, B.-J., Kim, T.-Y., Lee, S.-T., et al. (2002). Endostatin blocks vascular endothelial growth factor-mediated signaling via direct interaction with KDR/Flk-1. The Journal of Biological Chemistry, 277(31), 27872–27879. https://doi.org/10.1074/jbc.M202771200.

    Article  PubMed  CAS  Google Scholar 

  178. Hanai, J., Dhanabal, M., Karumanchi, S. A., Albanese, C., Waterman, M., Chan, B., et al. (2002). Endostatin causes G1 arrest of endothelial cells through inhibition of cyclin D1. Journal of Biological Chemistry, 277(19), 16464–16469. https://doi.org/10.1074/jbc.M112274200.

    Article  PubMed  CAS  Google Scholar 

  179. Bagley, R. G. (2010). The tumor microenvironment. Springer Science & Business Media.

  180. Raglow, Z., & Thomas, S. M. (2015). Tumor matrix protein collagen XIα1 in cancer. Cancer Letters, 357(2), 448–453. https://doi.org/10.1016/j.canlet.2014.12.011.

    Article  PubMed  CAS  Google Scholar 

  181. Vázquez-Villa, F., García-Ocaña, M., Galván, J. A., García-Martínez, J., García-Pravia, C., Menéndez-Rodríguez, P., et al. (2015). COL11A1/(pro)collagen 11A1 expression is a remarkable biomarker of human invasive carcinoma-associated stromal cells and carcinoma progression. Tumour Biology: The Journal of the International Society for Oncodevelopmental Biology and Medicine, 36(4), 2213–2222. https://doi.org/10.1007/s13277-015-3295-4.

    Article  CAS  Google Scholar 

  182. Kim, H., Watkinson, J., Varadan, V., & Anastassiou, D. (2010). Multi-cancer computational analysis reveals invasion-associated variant of desmoplastic reaction involving INHBA, THBS2 and COL11A1. BMC Medical Genomics, 3(1), 51. https://doi.org/10.1186/1755-8794-3-51.

    Article  PubMed  PubMed Central  Google Scholar 

  183. Chong, I.-W., Chang, M.-Y., Chang, H.-C., Yu, Y.-P., Sheu, C.-C., Tsai, J.-R., et al. (2006). Great potential of a panel of multiple hMTH1, SPD, ITGA11 and COL11A1 markers for diagnosis of patients with non-small cell lung cancer. Oncology Reports, 16(5), 981–988.

    PubMed  CAS  Google Scholar 

  184. Ewald, J. A., Downs, T. M., Cetnar, J. P., & Ricke, W. A. (2013). Expression microarray meta-analysis identifies genes associated with Ras/MAPK and related pathways in progression of muscle-invasive bladder transition cell carcinoma. PLoS One, 8(2), e55414. https://doi.org/10.1371/journal.pone.0055414.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  185. Cheon, D.-J., Tong, Y., Sim, M.-S., Dering, J., Berel, D., Cui, X., et al. (2014). A collagen-remodeling gene signature regulated by TGF-β signaling is associated with metastasis and poor survival in serous ovarian cancer. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 20(3), 711–723. https://doi.org/10.1158/1078-0432.CCR-13-1256.

    Article  CAS  Google Scholar 

  186. Suceveanu, A. I., Suceveanu, A., Voinea, F., Mazilu, L., Mixici, F., & Adam, T. (2009). Introduction of cytogenetic tests in colorectal cancer screening. Journal of gastrointestinal and liver diseases: JGLD, 18(1), 33–38.

    PubMed  Google Scholar 

  187. Fischer, H., Salahshor, S., Stenling, R., Björk, J., Lindmark, G., Iselius, L., et al. (2001). COL11A1 in FAP polyps and in sporadic colorectal tumors. BMC Cancer, 1, 17. https://doi.org/10.1186/1471-2407-1-17.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  188. Iizasa, T., Chang, H., Suzuki, M., Otsuji, M., Yokoi, S., Chiyo, M., et al. (2004). Overexpression of collagen XVIII is associated with poor outcome and elevated levels of circulating serum endostatin in non-small cell lung cancer. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 10(16), 5361–5366. https://doi.org/10.1158/1078-0432.CCR-04-0443.

    Article  CAS  Google Scholar 

  189. Hu, T.-H., Huang, C.-C., Wu, C.-L., Lin, P.-R., Liu, S.-Y., Lin, J.-W., et al. (2005). Increased endostatin/collagen XVIII expression correlates with elevated VEGF level and poor prognosis in hepatocellular carcinoma. Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc, 18(5), 663–672. https://doi.org/10.1038/modpathol.3800336.

    Article  CAS  Google Scholar 

  190. Thangavelu, P. U., Krenács, T., Dray, E., & Duijf, P. H. G. (2016). In epithelial cancers, aberrant COL17A1 promoter methylation predicts its misexpression and increased invasion. Clinical Epigenetics, 8(1), 120. https://doi.org/10.1186/s13148-016-0290-6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  191. Parikka, M., Kainulainen, T., Tasanen, K., Väänänen, A., Bruckner-Tuderman, L., & Salo, T. (2003). Alterations of collagen XVII expression during transformation of oral epithelium to dysplasia and carcinoma. The Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society, 51(7), 921–929. https://doi.org/10.1177/002215540305100707.

    Article  CAS  Google Scholar 

  192. Chen, I. M., Willumsen, N., Dehlendorff, C., Johansen, A. Z., Jensen, B. V., Hansen, C. P., et al. (2019). Clinical value of serum hyaluronan and propeptide of type III collagen in patients with pancreatic cancer. International Journal of Cancer. https://doi.org/10.1002/ijc.32751.

  193. Banys-Paluchowski, M., Loibl, S., Witzel, I., Mundhenke, C., Lederer, B., Solbach, C., et al. (2019). Clinical relevance of collagen protein degradation markers C3M and C4M in the serum of breast cancer patients treated with neoadjuvant therapy in the GeparQuinto trial. Cancers, 11(8). https://doi.org/10.3390/cancers11081186.

  194. Lipton, A., Leitzel, K., Ali, S. M., Polimera, H. V., Nagabhairu, V., Marks, E., et al. (2018). High turnover of extracellular matrix reflected by specific protein fragments measured in serum is associated with poor outcomes in two metastatic breast cancer cohorts. International Journal of Cancer, 143(11), 3027–3034. https://doi.org/10.1002/ijc.31627.

    Article  PubMed  CAS  Google Scholar 

  195. Kehlet, S. N., Sanz-Pamplona, R., Brix, S., Leeming, D. J., Karsdal, M. A., & Moreno, V. (2016). Excessive collagen turnover products are released during colorectal cancer progression and elevated in serum from metastatic colorectal cancer patients. Scientific Reports, 6(1), 1–7. https://doi.org/10.1038/srep30599.

    Article  CAS  Google Scholar 

  196. Ali, S. M., Demers, L. M., Leitzel, K., Harvey, H. A., Clemens, D., Mallinak, N., et al. (2004). Baseline serum NTx levels are prognostic in metastatic breast cancer patients with bone-only metastasis. Annals of Oncology: Official Journal of the European Society for Medical Oncology, 15(3), 455–459. https://doi.org/10.1093/annonc/mdh089.

    Article  CAS  Google Scholar 

  197. Ylisirniö, S., Höyhtyä, M., Mäkitaro, R., Pääakkö, P., Risteli, J., Kinnula, V. L., et al. (2001). Elevated serum levels of type I collagen degradation marker ICTP and tissue inhibitor of metalloproteinase (TIMP) 1 are associated with poor prognosis in lung cancer. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 7(6), 1633–1637.

    Google Scholar 

  198. Akimoto, S., Inomiya, H., Furuya, Y., Akakura, K., & Ito, H. (1998). Prognostic value of the serum levels of bone formation and bone resorption markers in prostate cancer patients with bone metastasis. European Urology, 34(2), 142–147. https://doi.org/10.1159/000019700.

    Article  PubMed  CAS  Google Scholar 

  199. Xu, S., Xu, H., Wang, W., Li, S., Li, H., Li, T., et al. (2019). The role of collagen in cancer: from bench to bedside. Journal of Translational Medicine, 17(1), 309. https://doi.org/10.1186/s12967-019-2058-1.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  200. Zhong, S., Jeong, J.-H., Chen, Z., Chen, Z., & Luo, J.-L. (2020). Targeting tumor microenvironment by small-molecule inhibitors. Translational Oncology, 13(1), 57–69. https://doi.org/10.1016/j.tranon.2019.10.001.

    Article  PubMed  CAS  Google Scholar 

  201. Li, M., Li, M., Yin, T., Shi, H., Wen, Y., Zhang, B., et al. (2016). Targeting of cancer-associated fibroblasts enhances the efficacy of cancer chemotherapy by regulating the tumor microenvironment. Molecular Medicine Reports, 13(3), 2476–2484. https://doi.org/10.3892/mmr.2016.4868.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  202. Mertens, J. C., Fingas, C. D., Christensen, J. D., Smoot, R. L., Bronk, S. F., Werneburg, N. W., et al. (2013). Therapeutic effects of deleting cancer-associated fibroblasts in cholangiocarcinoma. Cancer Research, 73(2), 897–907. https://doi.org/10.1158/0008-5472.CAN-12-2130.

    Article  PubMed  CAS  Google Scholar 

  203. Cleary, J. M., Lima, C. M. S. R., Hurwitz, H. I., Montero, A. J., Franklin, C., Yang, J., et al. (2014). A phase I clinical trial of navitoclax, a targeted high-affinity Bcl-2 family inhibitor, in combination with gemcitabine in patients with solid tumors. Investigational New Drugs, 32(5), 937–945. https://doi.org/10.1007/s10637-014-0110-9.

    Article  PubMed  CAS  Google Scholar 

  204. Karasic, T. B., O’Hara, M. H., Loaiza-Bonilla, A., Reiss, K. A., Teitelbaum, U. R., Borazanci, E., et al. (2019). Effect of gemcitabine and nab-Paclitaxel with or without hydroxychloroquine on patients with advanced pancreatic cancer: a phase 2 randomized clinical trial. JAMA Oncology, 5(7), 993–998. https://doi.org/10.1001/jamaoncol.2019.0684.

    Article  PubMed  PubMed Central  Google Scholar 

  205. Diop-Frimpong, B., Chauhan, V. P., Krane, S., Boucher, Y., & Jain, R. K. (2011). Losartan inhibits collagen I synthesis and improves the distribution and efficacy of nanotherapeutics in tumors. Proceedings of the National Academy of Sciences of the United States of America, 108(7), 2909–2914. https://doi.org/10.1073/pnas.1018892108.

    Article  PubMed  PubMed Central  Google Scholar 

  206. Cun, X., Ruan, S., Chen, J., Zhang, L., Li, J., He, Q., & Gao, H. (2016). A dual strategy to improve the penetration and treatment of breast cancer by combining shrinking nanoparticles with collagen depletion by losartan. Acta Biomaterialia, 31, 186–196. https://doi.org/10.1016/j.actbio.2015.12.002.

    Article  PubMed  CAS  Google Scholar 

  207. Murphy, J. E., Wo, J. Y., Ryan, D. P., Clark, J. W., Jiang, W., Yeap, B. Y., et al. (2019). Total neoadjuvant therapy with FOLFIRINOX in combination with losartan followed by chemoradiotherapy for locally advanced pancreatic cancer: a phase 2 clinical trial. JAMA Oncology, 5(7), 1020–1027. https://doi.org/10.1001/jamaoncol.2019.0892.

    Article  PubMed  PubMed Central  Google Scholar 

  208. Lee, K., Molenaar, R. J., Klaassen, R., Bijlsma, M. J., Weterman, M. J., Richel, D. J., et al. (2017). A Phase I study of LDE225 in combination with gemcitabine and nab-paclitaxel in patients with metastasized pancreatic cancer. Annals of Oncology. https://doi.org/10.1093/annonc/mdx369.143.

  209. Yamamura, S., Matsumura, N., Mandai, M., Huang, Z., Oura, T., Baba, T., et al. (2012). The activated transforming growth factor-beta signaling pathway in peritoneal metastases is a potential therapeutic target in ovarian cancer. International Journal of Cancer, 130(1), 20–28. https://doi.org/10.1002/ijc.25961.

    Article  PubMed  CAS  Google Scholar 

  210. Hau, P., Jachimczak, P., Schlingensiepen, R., Schulmeyer, F., Jauch, T., Steinbrecher, A., et al. (2007). Inhibition of TGF-beta2 with AP 12009 in recurrent malignant gliomas: from preclinical to phase I/II studies. Oligonucleotides, 17(2), 201–212. https://doi.org/10.1089/oli.2006.0053.

    Article  PubMed  CAS  Google Scholar 

  211. Hwang, L., Ng, K., Wang, W., & Trieu, V. N. (n.d.). An anti-TGF-beta-2 antisense primed tumors to subsequent chemotherapies. Journal of Clinical Oncology. 185. https://doi.org/10.1200/JCO.2016.34.15_suppl.e15727

  212. Hoffman, A., Qadri, B., Frant, J., Katz, Y., Bhusare, S. R., Breuer, E., et al. (2008). Carbamoylphosphonate matrix metalloproteinase inhibitors 6: cis-2-aminocyclohexylcarbamoylphosphonic acid, a novel orally active antimetastatic matrix metalloproteinase-2 selective inhibitor—synthesis and pharmacodynamic and pharmacokinetic analysis. Journal of Medicinal Chemistry, 51(5), 1406–1414. https://doi.org/10.1021/jm701087n.

    Article  PubMed  CAS  Google Scholar 

  213. Dufour, A., Sampson, N. S., Li, J., Kuscu, C., Rizzo, R. C., Deleon, J. L., et al. (2011). Small-molecule anticancer compounds selectively target the hemopexin domain of matrix metalloproteinase-9. Cancer Research, 71(14), 4977–4988. https://doi.org/10.1158/0008-5472.CAN-10-4552.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  214. Liang, H., Li, X., Chen, B., Wang, B., Zhao, Y., Zhuang, Y., et al. (2015). A collagen-binding EGFR single-chain Fv antibody fragment for the targeted cancer therapy. Journal of Controlled Release: Official Journal of the Controlled Release Society, 209, 101–109. https://doi.org/10.1016/j.jconrel.2015.04.029.

    Article  CAS  Google Scholar 

  215. Ishihara, J., Ishihara, A., Sasaki, K., Lee, S. S.-Y., Williford, J.-M., Yasui, M., et al. (2019). Targeted antibody and cytokine cancer immunotherapies through collagen affinity. Science Translational Medicine, 11(487). https://doi.org/10.1126/scitranslmed.aau3259.

  216. Brennen, W. N., Rosen, D. M., Wang, H., Isaacs, J. T., & Denmeade, S. R. (2012). Targeting carcinoma-associated fibroblasts within the tumor stroma with a fibroblast activation protein-activated prodrug. Journal of the National Cancer Institute, 104(17), 1320–1334. https://doi.org/10.1093/jnci/djs336.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  217. Sun, Z., Li, R., Sun, J., Peng, Y., **ao, L., Zhang, X., et al. (2017). Matrix metalloproteinase cleavable nanoparticles for tumor microenvironment and tumor cell dual-targeting drug delivery. ACS Applied Materials & Interfaces, 9(46), 40614–40627. https://doi.org/10.1021/acsami.7b11614.

    Article  CAS  Google Scholar 

  218. Egeblad, M., Nakasone, E. S., & Werb, Z. (2010). Tumors as organs: complex tissues that interface with the entire organism. Developmental Cell, 18(6), 884–901. https://doi.org/10.1016/j.devcel.2010.05.012.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  219. Wang, H., Mislati, R., Ahmed, R., Vincent, P., Nwabunwanne, S. F., Gunn, J. R., et al. (2019). Elastography can map the local inverse relationship between shear modulus and drug delivery within the pancreatic ductal adenocarcinoma microenvironment. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 25(7), 2136–2143. https://doi.org/10.1158/1078-0432.CCR-18-2684.

    Article  CAS  Google Scholar 

  220. Li, X., Shepard, H. M., Cowell, J. A., Zhao, C., Osgood, R. J., Rosengren, S., et al. (2018). Parallel accumulation of tumor hyaluronan, collagen, and other drivers of tumor progression. Clinical Cancer Research, 24(19), 4798–4807. https://doi.org/10.1158/1078-0432.CCR-17-3284.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  221. Gonçalves-Ribeiro, S., Sanz-Pamplona, R., Vidal, A., Sanjuan, X., Guillen Díaz-Maroto, N., Soriano, A., et al. (2017). Prediction of pathological response to neoadjuvant treatment in rectal cancer with a two-protein immunohistochemical score derived from stromal gene-profiling. Annals of Oncology: Official Journal of the European Society for Medical Oncology, 28(9), 2160–2168. https://doi.org/10.1093/annonc/mdx293.

Download references

Author information

Author notes

  1. Ana C. Martins Cavaco and Sara Dâmaso contributed equally to this work.

Authors and Affiliations

  1. Luis Costa Lab, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, 1649-028, Lisboa, Portugal

    Ana C. Martins Cavaco, Sandra Casimiro & Luís Costa

  2. Serviço de Oncologia, Hospital de Santa Maria-CHULN, 1649-028, Lisboa, Portugal

    Sara Dâmaso & Luís Costa

Authors
  1. Ana C. Martins Cavaco
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sara Dâmaso
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sandra Casimiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Luís Costa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Luís Costa.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Martins Cavaco, A.C., Dâmaso, S., Casimiro, S. et al. Collagen biology making inroads into prognosis and treatment of cancer progression and metastasis. Cancer Metastasis Rev 39, 603–623 (2020). https://doi.org/10.1007/s10555-020-09888-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10555-020-09888-5

Keywords

Search

Navigation