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Prognostic relevance of collagen XVIII expression in metastatic gastric carcinoma

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Tumor Biology

Abstract

Collagen XVIII is a component of vascular and epithelial basement membranes. The C-terminal fragment of the protein is termed endostatin, and is a potent inhibitor of angiogenesis. No reports on the clinical implications of collagen XVIII expression in human gastric cancer are currently available. Here, we investigate the clinical significance of collagen XVIII expression in gastric cancer. Seven gastric cancer cell lines were subjected to Western blotting. Collagen XVIII expression was examined in 118 gastric carcinoma tissues via immunohistochemistry. Western blotting revealed the presence of the 22-kDa collagen XVIII protein in four of seven gastric cancer cell lines. Immunohistochemistry detected collagen XVIII expression in the tumor cytoplasm in 115 of 118 gastric carcinoma patients (97%). No correlation was evident between collagen XVIII expression score and clinicopathologic findings when all patients were considered together. However, on subgroup analysis, 42 of 70 patients with distant metastasis were classified into low or moderate collagen XVIII expression groups, whereas the remaining 28 patients were grouped as showing high collagen XVIII expression. The prognosis for patients with high collagen XVIII-expressing gastric carcinoma was significantly worse than that for patients displaying low or moderate collagen XVIII expression (median survival time, 7.8 months vs. 18.3 months [log-rank, p = 0.01]; median time to progression, 3 months vs. 8 months [log-rank, p = 0.01]). High expression of collagen XVIII is associated with poor prognosis in patients with metastatic gastric carcinoma. Further studies on larger patient populations are warranted to validate the utility of collagen XVIII as a prognostic biomarker in gastric carcinoma.

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References

  1. Folkman J, Merler E, Abernathy C, Williams G. Isolation of a tumor factor responsible for angiogenesis. J Exp Med. 1971;133:275–88.

    Article  CAS  PubMed  Google Scholar 

  2. Folkman J. Angiogenesis inhibitors generated by tumors. Mol Med. 1995;1:120–2.

    CAS  PubMed  Google Scholar 

  3. Sottile J. Regulation of angiogenesis by extracellular matrix. Biochim Biophys Acta. 2004;1654:13–22.

    CAS  PubMed  Google Scholar 

  4. Saarela J, Rehn M, Oikarinen A, et al. The short and long forms of type XVIII collagen show clear tissue specificities in their expression and location in basement membrane zones in humans. Am J Pathol. 1998;153:611–26.

    CAS  PubMed  Google Scholar 

  5. Iozzo RV, Zoeller JJ, Nystrom A. Basement membrane proteoglycans: modulators par excellence of cancer growth and angiogenesis. Mol Cells. 2009;27:503–13.

    Article  CAS  PubMed  Google Scholar 

  6. Saarela J, Ylikarppa R, Rehn M, et al. Complete primary structure of two variant forms of human type XVIII collagen and tissue-specific differences in the expression of the corresponding transcripts. Matrix Biol. 1998;16:319–28.

    Article  CAS  PubMed  Google Scholar 

  7. Sasaki T, Fukai N, Mann K, et al. Structure, function and tissue forms of the C-terminal globular domain of collagen XVIII containing the angiogenesis inhibitor endostatin. Embo J. 1998;17:4249–56.

    Article  CAS  PubMed  Google Scholar 

  8. O’Reilly MS, Boehm T, Shing Y, et al. Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell. 1997;88:277–85.

    Article  PubMed  Google Scholar 

  9. Kulke MH, Bergsland EK, Ryan DP, et al. Phase II study of recombinant human endostatin in patients with advanced neuroendocrine tumors. J Clin Oncol. 2006;24:3555–61.

    Article  CAS  PubMed  Google Scholar 

  10. Feldman AL, Alexander Jr HR, Yang JC, et al. Prospective analysis of circulating endostatin levels in patients with renal cell carcinoma. Cancer. 2002;95:1637–43.

    Article  CAS  PubMed  Google Scholar 

  11. Bono P, Teerenhovi L, Joensuu H. Elevated serum endostatin is associated with poor outcome in patients with non-Hodgkin lymphoma. Cancer. 2003;97:2767–75.

    Article  CAS  PubMed  Google Scholar 

  12. Feldman AL, Tamarkin L, Paciotti GF, et al. Serum endostatin levels are elevated and correlate with serum vascular endothelial growth factor levels in patients with stage IV clear cell renal cancer. Clin Cancer Res. 2000;6:4628–34.

    CAS  PubMed  Google Scholar 

  13. Hu TH, Huang CC, Wu CL, et al. Increased endostatin/collagen XVIII expression correlates with elevated VEGF level and poor prognosis in hepatocellular carcinoma. Mod Pathol. 2005;18:663–72.

    Article  CAS  PubMed  Google Scholar 

  14. Iizasa T, Chang H, Suzuki M, et al. Overexpression of collagen XVIII is associated with poor outcome and elevated levels of circulating serum endostatin in non-small cell lung cancer. Clin Cancer Res. 2004;10:5361–6.

    Article  CAS  PubMed  Google Scholar 

  15. Suzuki M, Iizasa T, Ko E, et al. Serum endostatin correlates with progression and prognosis of non-small cell lung cancer. Lung Cancer. 2002;35:29–34.

    Article  PubMed  Google Scholar 

  16. Feldman AL, Pak H, Yang JC, et al. Serum endostatin levels are elevated in patients with soft tissue sarcoma. Cancer. 2001;91:1525–9.

    Article  CAS  PubMed  Google Scholar 

  17. Feldman AL, Alexander Jr HR, Bartlett DL, et al. A prospective analysis of plasma endostatin levels in colorectal cancer patients with liver metastases. Ann Surg Oncol. 2001;8:741–5.

    Article  CAS  PubMed  Google Scholar 

  18. Woo IS, Kim KA, Jeon HM, et al. Pretreatment serum endostatin as a prognostic indicator in metastatic gastric carcinoma. Int J Cancer. 2006;119:2901–6.

    Article  CAS  PubMed  Google Scholar 

  19. Chang H, Iizasa T, Shibuya K, et al. Increased expression of collagen XVIII and its prognostic value in nonsmall cell lung carcinoma. Cancer. 2004;100:1665–72.

    Article  CAS  PubMed  Google Scholar 

  20. Musso O, Rehn M, Theret N, et al. Tumor progression is associated with a significant decrease in the expression of the endostatin precursor collagen XVIII in human hepatocellular carcinomas. Cancer Res. 2001;61:45–9.

    CAS  PubMed  Google Scholar 

  21. Wen W, Moses MA, Wiederschain D, et al. The generation of endostatin is mediated by elastase. Cancer Res. 1999;59:6052–6.

    CAS  PubMed  Google Scholar 

  22. Guenther U, Herbst H, Bauer M, et al. Collagen type XVIII/endostatin is differentially expressed in primary and metastatic colorectal cancers and ovarian carcinomas. Br J Cancer. 2001;85:1540–5.

    Article  CAS  PubMed  Google Scholar 

  23. Heljasvaara R, Nyberg P, Luostarinen J, et al. Generation of biologically active endostatin fragments from human collagen XVIII by distinct matrix metalloproteases. Exp Cell Res. 2005;307:292–304.

    Article  CAS  PubMed  Google Scholar 

  24. Felbor U, Dreier L, Bryant RA, et al. Secreted cathepsin L generates endostatin from collagen XVIII. EMBO J. 2000;19:1187–94.

    Article  CAS  PubMed  Google Scholar 

  25. Unemori EN, Ferrara N, Bauer EA, Amento EP. Vascular endothelial growth factor induces interstitial collagenase expression in human endothelial cells. J Cell Physiol. 1992;153:557–62.

    Article  CAS  PubMed  Google Scholar 

  26. Zucker S, Mirza H, Conner CE, et al. Vascular endothelial growth factor induces tissue factor and matrix metalloproteinase production in endothelial cells: conversion of prothrombin to thrombin results in progelatinase A activation and cell proliferation. Int J Cancer. 1998;75:780–6.

    Article  CAS  PubMed  Google Scholar 

  27. Ohlund D, Ardnor B, Oman M, et al. Expression pattern and circulating levels of endostatin in patients with pancreas cancer. Int J Cancer. 2008;122:2805–10.

    Article  PubMed  Google Scholar 

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Acknowledgments

This work was accomplished, in part, with financial support from St. Mary's Hospital of the Catholic University in 2008, and a grant from the Ministry of Health & Welfare, Republic of Korea, Metropolitan University Specialization Projects, in 2008. We are grateful to Jung-A Kim for collecting clinical data and to In Kyung Kwon for technical assistance.

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Correspondence to In Sook Woo.

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Kyu Sang Lee and Gyeong Sin Park are equal contributors

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Lee, K.S., Park, G.S., Hong, S.H. et al. Prognostic relevance of collagen XVIII expression in metastatic gastric carcinoma. Tumor Biol. 31, 165–170 (2010). https://doi.org/10.1007/s13277-010-0022-z

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  • DOI: https://doi.org/10.1007/s13277-010-0022-z

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