Modeling Cancer Metastasis

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Patient-Derived Xenograft Models of Human Cancer

Part of the book series: Molecular and Translational Medicine ((MOLEMED))

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Abstract

Cancer metastases constitute a therapy-resistant stage in most cases; thus, the study of mechanisms underlying the metastatic process is a subject of intense research. With the recognition of patient-derived xenografts (PDXs) as being clinically relevant, in this chapter we describe methods to model specific stages of the metastatic cascade using PDXs. In particular we emphasize the processing of PDXs for in vitro studies to investigate migration, invasion, and cancer cell-stromal cell interaction. In vivo, we describe methods to implant cancer cells into the left ventricle (to study dissemination of cancer cells in the blood stream while bypassing the initial steps of metastases) and the direct implantation of cancer cells in the femur of immunodeficient mice (for cancer cell-bone interaction and preclinical studies). We also describe methods to evaluate these in vivo assays and outline basic concepts and methods of intravital microscopy to study early stages of metastases.

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Abbreviations

3D:

Three dimensional

cPDXs:

Cancer cells derived from PDXs

ECM:

Extracellular matrix

PBS:

Phosphate-buffered saline

PCa:

Prostate cancer

PDXs:

Patient-derived xenografts

UICC:

Union for International Cancer Control

References

  1. Talmadge JE, Fidler IJ. AACR centennial series: the biology of cancer metastasis: historical perspective. Cancer Res. 2010;70(14):5649–69. doi:10.1158/0008-5472.CAN-10-1040.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Massague J, Obenauf AC. Metastatic colonization by circulating tumour cells. Nature. 2016;529(7586):298–306. doi:10.1038/nature17038.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Sethi N, Kang Y. Unravelling the complexity of metastasis—molecular understanding and targeted therapies. Nat Rev Cancer. 2011;11(10):735–48. doi:10.1038/nrc3125.

    Article  CAS  PubMed  Google Scholar 

  4. Turajlic S, Swanton C. Metastasis as an evolutionary process. Science. 2016;352(6282):169–75. doi:10.1126/science.aaf2784.

    Article  CAS  PubMed  Google Scholar 

  5. Valastyan S, Weinberg RA. Tumor metastasis: molecular insights and evolving paradigms. Cell. 2011;147(2):275–92. doi:10.1016/j.cell.2011.09.024.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Hart IR, Fidler IJ. Role of organ selectivity in the determination of metastatic patterns of B16 melanoma. Cancer Res. 1980;40(7):2281–7.

    CAS  PubMed  Google Scholar 

  7. Catalona WJ. Management of cancer of the prostate. N Engl J Med. 1994;331(15):996–1004.

    Article  CAS  PubMed  Google Scholar 

  8. Cook GB, Watson FR. Events in the natural history of prostate cancer: using salvage curves, mean age distributions and contingency coefficients. J Urol. 1968;96:87–96.

    Google Scholar 

  9. Loberg RD, Logothetis CJ, Keller ET, Pienta KJ. Pathogenesis and treatment of prostate cancer bone metastases: targeting the lethal phenotype. J Clin Oncol. 2005;23(32):8232–41.

    Article  CAS  PubMed  Google Scholar 

  10. Taichman RS, Wang Z, Shiozawa Y, Jung Y, Song J, Balduino A, et al. Prospective identification and skeletal localization of cells capable of multilineage differentiation in vivo. Stem Cells Dev. 2010;19(10):1557–70. doi:10.1089/scd.2009.0445.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Decker AM, Jung Y, Cackowski F, Taichman RS. The role of hematopoietic stem cell niche in prostate cancer bone metastasis. J Bone Oncol. 2016;5(3):117–20. doi:10.1016/j.jbo.2016.02.005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Shiozawa Y, Pedersen EA, Havens AM, Jung Y, Mishra A, Joseph J, et al. Human prostate cancer metastases target the hematopoietic stem cell niche to establish footholds in mouse bone marrow. J Clin Invest. 2011;121(4):1298–312. doi:10.1172/JCI43414.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Beltran H, Tomlins S, Aparicio A, Arora V, Rickman D, Ayala G, et al. Aggressive variants of castration-resistant prostate cancer. Clin Cancer Res. 2014;20(11):2846–50. doi:10.1158/1078-0432.CCR-13-3309.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Gleason DF. Classification of prostatic carcinomas. Cancer Chemother Rep. 1966;50(3):125–8.

    CAS  PubMed  Google Scholar 

  15. Logothetis CJ, Gallick GE, Maity SN, Kim J, Aparicio A, Efstathiou E, et al. Molecular classification of prostate cancer progression: foundation for marker-driven treatment of prostate cancer. Cancer Discov. 2013;3(8):849–61. doi:10.1158/2159-8290.CD-12-0460.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Hong MK, Macintyre G, Wedge DC, Van Loo P, Patel K, Lunke S, et al. Tracking the origins and drivers of subclonal metastatic expansion in prostate cancer. Nat Commun. 2015;6:6605. doi:10.1038/ncomms7605.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Crockford A, Jamal-Hanjani M, Hicks J, Swanton C. Implications of intratumour heterogeneity for treatment stratification. J Pathol. 2014;232(2):264–73. doi:10.1002/path.4270.

    Article  PubMed  Google Scholar 

  18. de Bruin EC, McGranahan N, Mitter R, Salm M, Wedge DC, Yates L, et al. Spatial and temporal diversity in genomic instability processes defines lung cancer evolution. Science. 2014;346(6206):251–6. doi:10.1126/science.1253462.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Li ZG, Mathew P, Yang J, Starbuck MW, Zurita AJ, Liu J, et al. Androgen receptor-negative human prostate cancer cells induce osteogenesis in mice through FGF9-mediated mechanisms. J Clin Invest. 2008a;118(8):2697–710. doi:10.1172/JCI33093.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Roychowdhury S, Iyer MK, Robinson DR, Lonigro RJ, Wu YM, Cao X, et al. Personalized oncology through integrative high-throughput sequencing: a pilot study. Sci Transl Med. 2011;3(111):111ra21. doi:10.1126/scitranslmed.3003161.

    Article  Google Scholar 

  21. Tzelepi V, Zhang J, Lu JF, Kleb B, Wu G, Wan X, et al. Modeling a lethal prostate cancer variant with small-cell carcinoma features. Clin Cancer Res. 2012;18(3):666–77. doi:10.1158/1078-0432.CCR-11-1867.

    Article  CAS  PubMed  Google Scholar 

  22. Aparicio A, Tzelepi V, Araujo JC, Guo CC, Liang S, Troncoso P, et al. Neuroendocrine prostate cancer xenografts with large-cell and small-cell features derived from a single patient’s tumor: morphological, immunohistochemical, and gene expression profiles. Prostate. 2011;71(8):846–56. doi:10.1002/pros.21301.

    Article  CAS  PubMed  Google Scholar 

  23. Brenner JC, Ateeq B, Li Y, Yocum AK, Cao Q, Asangani IA, et al. Mechanistic rationale for inhibition of poly(ADP-ribose) polymerase in ETS gene fusion-positive prostate cancer. Cancer Cell. 2011;19(5):664–78. doi:10.1016/j.ccr.2011.04.010.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Dafni H, Burghardt AJ, Majumdar S, Navone NM, Ronen SM. Vascular patterning and permeability in prostate cancer models with differing osteogenic properties. NMR Biomed. 2012;25(6):843–51. doi:10.1002/nbm.1800.

    Article  PubMed  Google Scholar 

  25. Dayyani F, Parikh NU, Varkaris AS, Song JH, Moorthy S, Chatterji T, et al. Combined inhibition of IGF-1R/IR and Src family kinases enhances antitumor effects in prostate cancer by decreasing activated survival pathways. PLoS One. 2012;7(12):e51189. doi:10.1371/journal.pone.0051189.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Fong EL, Martinez M, Yang J, Mikos AG, Navone NM, Harrington DA, et al. Hydrogel-based 3D model of patient-derived prostate xenograft tumors suitable for drug screening. Mol Pharm. 2014;11(7):2040–50. doi:10.1021/mp500085p.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Fong EL, Wan X, Yang J, Morgado M, Mikos AG, Harrington DA, et al. A 3D in vitro model of patient-derived prostate cancer xenograft for controlled interrogation of in vivo tumor-stromal interactions. Biomaterials. 2016;77:164–72. doi:10.1016/j.biomaterials.2015.10.059.

    Article  CAS  PubMed  Google Scholar 

  28. Karlou M, Lu JF, Wu G, Maity S, Tzelepi V, Navone NM, et al. Hedgehog signaling inhibition by the small molecule smoothened inhibitor GDC-0449 in the bone forming prostate cancer xenograft MDA PCa 118b. Prostate. 2012;72(15):1638–47. doi:10.1002/pros.22517.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Kundra V, Ng CS, Ma J, Bankson JA, Price RE, Cody DD, et al. In vivo imaging of prostate cancer involving bone in a mouse model. Prostate. 2007a;67(1):50–60. doi:10.1002/pros.20494.

    Article  PubMed  Google Scholar 

  30. Lee YC, Cheng CJ, Bilen MA, Lu JF, Satcher RL, Yu-Lee LY, et al. BMP4 promotes prostate tumor growth in bone through osteogenesis. Cancer Res. 2011;71(15):5194–203. doi:10.1158/0008-5472.CAN-10-4374.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Lee YC, Gajdosik MS, Josic D, Clifton JG, Logothetis C, Yu-Lee LY, et al. Secretome analysis of an osteogenic prostate tumor identifies complex signaling networks mediating cross-talk of cancer and stromal cells within the tumor microenvironment. Mol Cell Proteomics. 2015a;14(3):471–83. doi:10.1074/mcp.M114.039909.

    Article  CAS  PubMed  Google Scholar 

  32. Lee YC, Lin SC, Yu G, Cheng CJ, Liu B, Liu HC, et al. Identification of bone-derived factors conferring de novo therapeutic resistance in metastatic prostate cancer. Cancer Res. 2015b;75(22):4949–59. doi:10.1158/0008-5472.CAN-15-1215.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Li L, Chang W, Yang G, Ren C, Park S, Karantanos T, et al. Targeting poly(ADP-ribose) polymerase and the c-Myb-regulated DNA damage response pathway in castration-resistant prostate cancer. Sci Signal. 2014;7(326):ra47. doi:10.1126/scisignal.2005070.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Liu J, You P, Chen G, Fu X, Zeng X, Wang C, et al. Hyperactivated FRS2alpha-mediated signaling in prostate cancer cells promotes tumor angiogenesis and predicts poor clinical outcome of patients. Oncogene. 2015; doi:10.1038/onc.2015.239.

    Google Scholar 

  35. Mandelin J, Cardo-Vila M, Driessen WH, Mathew P, Navone NM, Lin SH, et al. Selection and identification of ligand peptides targeting a model of castrate-resistant osteogenic prostate cancer and their receptors. Proc Natl Acad Sci U S A. 2015;112(12):3776–81. doi:10.1073/pnas.1500128112.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Mohamedali KA, Li ZG, Starbuck MW, Wan X, Yang J, Kim S, et al. Inhibition of prostate cancer osteoblastic progression with VEGF121/rGel, a single agent targeting osteoblasts, osteoclasts, and tumor neovasculature. Clin Cancer Res. 2011;17(8):2328–38. doi:10.1158/1078-0432.CCR-10-2943.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Pasqualini R, Millikan RE, Christianson DR, Cardo-Vila M, Driessen WH, Giordano RJ, et al. Targeting the interleukin-11 receptor alpha in metastatic prostate cancer: a first-in-man study. Cancer. 2015; doi:10.1002/cncr.29344.

    PubMed  PubMed Central  Google Scholar 

  38. Prantl L, Muehlberg F, Navone NM, Song YH, Vykoukal J, Logothetis CJ, et al. Adipose tissue-derived stem cells promote prostate tumor growth. Prostate. 2010;70(15):1709–15. doi:10.1002/pros.21206.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Prensner JR, Chen W, Iyer MK, Cao Q, Ma T, Han S, et al. PCAT-1, a long noncoding RNA, regulates BRCA2 and controls homologous recombination in cancer. Cancer Res. 2014;74(6):1651–60. doi:10.1158/0008-5472.CAN-13-3159.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Salameh A, Lee AK, Cardo-Vila M, Nunes DN, Efstathiou E, Staquicini FI, et al. PRUNE2 is a human prostate cancer suppressor regulated by the intronic long noncoding RNA PCA3. Proc Natl Acad Sci U S A. 2015; doi:10.1073/pnas.1507882112.

    Google Scholar 

  41. Sircar K, Huang H, Hu L, Cogdell D, Dhillon J, Tzelepi V, et al. Integrative molecular profiling reveals asparagine synthetase is a target in castration-resistant prostate cancer. Am J Pathol. 2012a;180(3):895–903. doi:10.1016/j.ajpath.2011.11.030.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Sircar K, Huang H, Hu L, Liu Y, Dhillon J, Cogdell D, et al. Mitosis phase enrichment with identification of mitotic centromere-associated kinesin as a therapeutic target in castration-resistant prostate cancer. PLoS One. 2012b;7(2):e31259. doi:10.1371/journal.pone.0031259.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Wan X, Corn PG, Yang J, Palanisamy N, Starbuck MW, Efstathiou E, et al. Prostate cancer cell-stromal cell crosstalk via FGFR1 mediates antitumor activity of dovitinib in bone metastases. Sci Transl Med. 2014;6(252):252ra122. doi:10.1126/scitranslmed.3009332.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Wan X, Liu J, Lu JF, Tzelepi V, Yang J, Starbuck MW, et al. Activation of beta-catenin signaling in androgen receptor-negative prostate cancer cells. Clin Cancer Res. 2012;18(3):726–36. doi:10.1158/1078-0432.CCR-11-2521.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Petrie RJ, Doyle AD, Yamada KM. Random versus directionally persistent cell migration. Nat Rev Mol Cell Biol. 2009;10(8):538–49. doi:10.1038/nrm2729.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Provenzano PP, Inman DR, Eliceiri KW, Trier SM, Keely PJ. Contact guidance mediated three-dimensional cell migration is regulated by rho/ROCK-dependent matrix reorganization. Biophys J. 2008;95(11):5374–84. doi:10.1529/biophysj.108.133116.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Friedl P, Gilmour D. Collective cell migration in morphogenesis, regeneration and cancer. Nat Rev Mol Cell Biol. 2009;10(7):445–57. doi:10.1038/nrm2720.

    Article  CAS  PubMed  Google Scholar 

  48. Kohrman AQ, Matus DQ. Divide or conquer: cell cycle regulation of invasive behavior. Trends Cell Biol. 2016; doi:10.1016/j.tcb.2016.08.003.

    PubMed  Google Scholar 

  49. Hagedorn EJ, Ziel JW, Morrissey MA, Linden LM, Wang Z, Chi Q, et al. The netrin receptor DCC focuses invadopodia-driven basement membrane transmigration in vivo. J Cell Biol. 2013;201(6):903–13. doi:10.1083/jcb.201301091.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Matus DQ, Li XY, Durbin S, Agarwal D, Chi Q, Weiss SJ, et al. In vivo identification of regulators of cell invasion across basement membranes. Sci Signal. 2010;3(120):ra35. doi:10.1126/scisignal.2000654.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Matus DQ, Lohmer LL, Kelley LC, Schindler AJ, Kohrman AQ, Barkoulas M, et al. Invasive cell fate requires G1 cell-cycle arrest and histone deacetylase-mediated changes in gene expression. Dev Cell. 2015;35(2):162–74. doi:10.1016/j.devcel.2015.10.002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Drost J, Karthaus WR, Gao D, Driehuis E, Sawyers CL, Chen Y, et al. Organoid culture systems for prostate epithelial and cancer tissue. Nat Protoc. 2016;11(2):347–58. doi:10.1038/nprot.2016.006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Gao D, Vela I, Sboner A, Iaquinta PJ, Karthaus WR, Gopalan A, et al. Organoid cultures derived from patients with advanced prostate cancer. Cell. 2014;159(1):176–87. doi:10.1016/j.cell.2014.08.016.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Justus CR, Leffler N, Ruiz-Echevarria M, Yang LV. In vitro cell migration and invasion assays. J Vis Exp. 2014;88 doi:10.3791/51046.

  55. Nobes CD, Hall A. Rho GTPases control polarity, protrusion, and adhesion during cell movement. J Cell Biol. 1999;144(6):1235–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Gaggioli C, Hooper S, Hidalgo-Carcedo C, Grosse R, Marshall JF, Harrington K, et al. Fibroblast-led collective invasion of carcinoma cells with differing roles for RhoGTPases in leading and following cells. Nat Cell Biol. 2007;9(12):1392–400. doi:10.1038/ncb1658.

    Article  CAS  PubMed  Google Scholar 

  57. Wolf K, Wu YI, Liu Y, Geiger J, Tam E, Overall C, et al. Multi-step pericellular proteolysis controls the transition from individual to collective cancer cell invasion. Nat Cell Biol. 2007;9(8):893–904. doi:10.1038/ncb1616.

    Article  CAS  PubMed  Google Scholar 

  58. Haycock JW. 3D cell culture: a review of current approaches and techniques. Methods Mol Biol. 2011;695:1–15. doi:10.1007/978-1-60761-984-0_1.

    Article  CAS  PubMed  Google Scholar 

  59. Truong D, Puleo J, Llave A, Mouneimne G, Kamm RD, Nikkhah M. Breast cancer cell invasion into a three dimensional tumor-stroma microenvironment. Sci Rep. 2016;6:34094. doi:10.1038/srep34094.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Kozlow W, Guise TA. Breast cancer metastasis to bone: mechanisms of osteolysis and implications for therapy. J Mammary Gland Biol Neoplasia. 2005;10(2):169–80. doi:10.1007/s10911-005-5399-8.

    Article  PubMed  Google Scholar 

  61. Logothetis CJ, Navone NM, Lin SH. Understanding the biology of bone metastases: key to the effective treatment of prostate cancer. Clin Cancer Res. 2008;14(6):1599–602. doi:10.1158/1078-0432.CCR-07-4603.

    Article  CAS  PubMed  Google Scholar 

  62. Yang J, Fizazi K, Peleg S, Sikes CR, Raymond AK, Jamal N, et al. Prostate cancer cells induce osteoblast differentiation through a Cbfa1-dependent pathway. Cancer Res. 2001;61(14):5652–9.

    CAS  PubMed  Google Scholar 

  63. Li ZG, Yang J, Vazquez ES, Rose D, Vakar-Lopez F, Mathew P, et al. Low-density lipoprotein receptor-related protein 5 (LRP5) mediates the prostate cancer-induced formation of new bone. Oncogene. 2008b;27(5):596–603. doi:10.1038/sj.onc.1210694.

    Article  CAS  PubMed  Google Scholar 

  64. Kim J, Yu W, Kovalski K, Ossowski L. Requirement for specific proteases in cancer cell intravasation as revealed by a novel semiquantitative PCR-based assay. Cell. 1998;94(3):353–62.

    Article  CAS  PubMed  Google Scholar 

  65. McClatchey AI. Modeling metastasis in the mouse. Oncogene. 1999;18(38):5334–9. doi:10.1038/sj.onc.1203086.

    Article  CAS  PubMed  Google Scholar 

  66. Quigley JP, Armstrong PB. Tumor cell intravasation alu-cidated: the chick embryo opens the window. Cell. 1998;94(3):281–4.

    Article  CAS  PubMed  Google Scholar 

  67. Brown KM, Xue A, Mittal A, Samra JS, Smith R, Hugh TJ. Patient-derived xenograft models of colorectal cancer in pre-clinical research: a systematic review. Oncotarget. 2016; doi:10.18632/oncotarget.11184.

    Google Scholar 

  68. Paez-Ribes M, Man S, Xu P, Kerbel RS. Development of patient derived xenograft models of overt spontaneous breast cancer metastasis: a cautionary note. PLoS One. 2016;11(6):e0158034. doi:10.1371/journal.pone.0158034.

    Article  PubMed  PubMed Central  Google Scholar 

  69. DeRose YS, Wang G, Lin YC, Bernard PS, Buys SS, Ebbert MT, et al. Tumor grafts derived from women with breast cancer authentically reflect tumor pathology, growth, metastasis and disease outcomes. Nat Med. 2011;17(11):1514–20. doi:10.1038/nm.2454.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Zhang X, Claerhout S, Prat A, Dobrolecki LE, Petrovic I, Lai Q, et al. A renewable tissue resource of phenotypically stable, biologically and ethnically diverse, patient-derived human breast cancer xenograft models. Cancer Res. 2013;73(15):4885–97. doi:10.1158/0008-5472.CAN-12-4081.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Rofstad EK, Huang R, Galappathi K, Andersen LM, Wegner CS, Hauge A, et al. Functional intratumoral lymphatics in patient-derived xenograft models of squamous cell carcinoma of the uterine cervix: implications for lymph node metastasis. Oncotarget. 2016; doi:10.18632/oncotarget.10931.

    Google Scholar 

  72. Chishima T, Miyagi Y, Wang X, Yamaoka H, Shimada H, Moossa AR, et al. Cancer invasion and micrometastasis visualized in live tissue by green fluorescent protein expression. Cancer Res. 1997;57(10):2042–7.

    CAS  PubMed  Google Scholar 

  73. Ellenbroek SI, van Rheenen J. Imaging hallmarks of cancer in living mice. Nat Rev Cancer. 2014;14(6):406–18. doi:10.1038/nrc3742.

    Article  CAS  PubMed  Google Scholar 

  74. Koop S, Schmidt EE, MacDonald IC, Morris VL, Khokha R, Grattan M, et al. Independence of metastatic ability and extravasation: metastatic ras-transformed and control fibroblasts extravasate equally well. Proc Natl Acad Sci U S A. 1996;93(20):11080–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Andresen V, Alexander S, Heupel WM, Hirschberg M, Hoffman RM, Friedl P. Infrared multiphoton microscopy: subcellular-resolved deep tissue imaging. Curr Opin Biotechnol. 2009;20(1):54–62. doi:10.1016/j.copbio.2009.02.008.

    Article  CAS  PubMed  Google Scholar 

  76. Condeelis J, Segall JE. Intravital imaging of cell movement in tumours. Nat Rev Cancer. 2003;3(12):921–30. doi:10.1038/nrc1231.

    Article  CAS  PubMed  Google Scholar 

  77. Sahai E, Wyckoff J, Philippar U, Segall JE, Gertler F, Condeelis J. Simultaneous imaging of GFP, CFP and collagen in tumors in vivo using multiphoton microscopy. BMC Biotechnol. 2005;5:14. doi:10.1186/1472-6750-5-14.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Wang BG, Riemann I, Schubert H, Schweitzer D, Konig K, Halbhuber KJ. Multiphoton microscopy for monitoring intratissue femtosecond laser surgery effects. Lasers Surg Med. 2007a;39(6):527–33. doi:10.1002/lsm.20523.

    Article  PubMed  Google Scholar 

  79. Wang W, Wyckoff JB, Frohlich VC, Oleynikov Y, Huttelmaier S, Zavadil J, et al. Single cell behavior in metastatic primary mammary tumors correlated with gene expression patterns revealed by molecular profiling. Cancer Res. 2002;62(21):6278–88.

    CAS  PubMed  Google Scholar 

  80. Vakoc BJ, Lanning RM, Tyrrell JA, Padera TP, Bartlett LA, Stylianopoulos T, et al. Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging. Nat Med. 2009;15(10):1219–23. doi:10.1038/nm.1971.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Evans CL, Potma EO, Puoris’haag M, Cote D, Lin CP, **e XS. Chemical imaging of tissue in vivo with video-rate coherent anti-stokes Raman scattering microscopy. Proc Natl Acad Sci U S A. 2005;102(46):16807–12. doi:10.1073/pnas.0508282102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Wyckoff JB, Jones JG, Condeelis JS, Segall JE. A critical step in metastasis: in vivo analysis of intravasation at the primary tumor. Cancer Res. 2000;60(9):2504–11.

    CAS  PubMed  Google Scholar 

  83. Wang W, Wyckoff JB, Goswami S, Wang Y, Sidani M, Segall JE, et al. Coordinated regulation of pathways for enhanced cell motility and chemotaxis is conserved in rat and mouse mammary tumors. Cancer Res. 2007b;67(8):3505–11. doi:10.1158/0008-5472.CAN-06-3714.

    Article  CAS  PubMed  Google Scholar 

  84. Romanelli E, Sorbara CD, Nikic I, Dagkalis A, Misgeld T, Kerschensteiner M. Cellular, subcellular and functional in vivo labeling of the spinal cord using vital dyes. Nat Protoc. 2013;8(3):481–90. doi:10.1038/nprot.2013.022.

    Article  CAS  PubMed  Google Scholar 

  85. Veiseh M, Kwon DH, Borowsky AD, Tolg C, Leong HS, Lewis JD, et al. Cellular heterogeneity profiling by hyaluronan probes reveals an invasive but slow-growing breast tumor subset. Proc Natl Acad Sci U S A. 2014;111(17):E1731–9. doi:10.1073/pnas.1402383111.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Dan S, Okamura M, Mukai Y, Yoshimi H, Inoue Y, Hanyu A, et al. ZSTK474, a specific phosphatidylinositol 3-kinase inhibitor, induces G1 arrest of the cell cycle in vivo. Eur J Cancer. 2012;48(6):936–43. doi:10.1016/j.ejca.2011.10.006.

    Article  CAS  PubMed  Google Scholar 

  87. Kedrin D, Gligorijevic B, Wyckoff J, Verkhusha VV, Condeelis J, Segall JE, et al. Intravital imaging of metastatic behavior through a mammary imaging window. Nat Methods. 2008;5(12):1019–21. doi:10.1038/nmeth.1269.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Wyckoff JB, Pinner SE, Gschmeissner S, Condeelis JS, Sahai E. ROCK- and myosin-dependent matrix deformation enables protease-independent tumor-cell invasion in vivo. Curr Biol. 2006;16(15):1515–23. doi:10.1016/j.cub.2006.05.065.

    Article  CAS  PubMed  Google Scholar 

  89. Lo Celso C, Lin CP, Scadden DT. In vivo imaging of transplanted hematopoietic stem and progenitor cells in mouse calvarium bone marrow. Nat Protoc. 2011;6(1):1–14. doi:10.1038/nprot.2010.168.

    Article  PubMed  Google Scholar 

  90. Mempel TR, Scimone ML, Mora JR, von Andrian UH. In vivo imaging of leukocyte trafficking in blood vessels and tissues. Curr Opin Immunol. 2004;16(4):406–17. doi:10.1016/j.coi.2004.05.018.

    Article  CAS  PubMed  Google Scholar 

  91. Egen JG, Rothfuchs AG, Feng CG, Horwitz MA, Sher A, Germain RN. Intravital imaging reveals limited antigen presentation and T cell effector function in mycobacterial granulomas. Immunity. 2011;34(5):807–19. doi:10.1016/j.immuni.2011.03.022.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Lee J, Li M, Milwid J, Dunham J, Vinegoni C, Gorbatov R, et al. Implantable microenvironments to attract hematopoietic stem/cancer cells. Proc Natl Acad Sci U S A. 2012;109(48):19638–43. doi:10.1073/pnas.1208384109.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Ravoori M, Czaplinska AJ, Sikes C, Han L, Johnson EM, Qiao W, et al. Quantification of mineralized bone response to prostate cancer by noninvasive in vivo microCT and non-destructive ex vivo microCT and DXA in a mouse model. PLoS One. 2010;5(3):e9854. doi:10.1371/journal.pone.0009854.

    Article  PubMed  PubMed Central  Google Scholar 

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Correspondence to Nora M. Navone .

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Navone, N.M., Labanca, E. (2017). Modeling Cancer Metastasis. In: Wang, Y., Lin, D., Gout, P. (eds) Patient-Derived Xenograft Models of Human Cancer . Molecular and Translational Medicine. Humana Press, Cham. https://doi.org/10.1007/978-3-319-55825-7_7

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