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A Prospective Analysis of Plasma Endostatin Levels in Colorectal Cancer Patients With Liver Metastases

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Abstract

Background: Circulating inhibitors of angiogenesis have been suggested to affect the growth of distant micrometastatic disease in patients with cancer. This study was designed to evaluate circulating endostatin levels in colorectal cancer patients with liver metastases.

Methods: Plasma samples from 30 colorectal cancer patients with liver metastases were analyzed for endostatin and vascular endothelial growth factor (VEGF) by using competitive enzyme immunoassays. Samples were compared with plasma from age- and sex-matched healthy controls; values >2 SD above the control mean were considered elevated.

Results: Plasma endostatin levels were significantly higher in the 30 cancer patients than controls (P < .0001) and correlated with preoperative VEGF levels (P = .0008). Eighteen patients underwent surgical treatment (liver resection, n = 10; or isolated hepatic perfusion with melphalan, n = 8). Seventeen treated patients were available for follow-up. Eight of 11 patients who progressed had elevated plasma endostatin levels at the time of progression. None of six patients who remained progression free had elevated endostatin levels at last follow-up (P = .02).

Conclusions: Plasma endostatin levels are elevated in colorectal cancer patients with liver metastases and correlate with VEGF levels. Elevated endostatin levels during follow-up are associated with disease progression. Understanding the role of endogenous endostatin in cancer patients may lead to novel strategies to inhibit tumor angiogenesis.

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References

  1. Landis SH, Murray T, Bolden S, Wingo PA. Cancer statistics, 1999. CA Cancer J Clin 1999; 49: 8–31.

    Article  PubMed  CAS  Google Scholar 

  2. Fong Y. Surgical therapy of hepatic colorectal metastasis. CA Cancer J Clin 1999; 49: 231–55.

    Article  PubMed  CAS  Google Scholar 

  3. Folkman J. What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst 1990; 82: 4–6.

    Article  PubMed  CAS  Google Scholar 

  4. 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 

  5. 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.

    PubMed  CAS  Google Scholar 

  6. Feldman AL, Pak H, Yang JC, Alexander HR, Libutti SK. Serum endostatin levels are elevated in patients with soft tissue sarcoma. Cancer 2001; 91: 1525–9.

    Article  PubMed  CAS  Google Scholar 

  7. Musso O, Rehn M, Saarela J, et al. Collagen XVIII is localized in sinusoids and basement membrane zones and expressed by hepatocytes and activated stellate cells in fibrotic human liver. Hepatology 1998; 28: 98–107.

    Article  PubMed  CAS  Google Scholar 

  8. Bartlett DL, Libutti SK, Figg WD, Fraker DL, Alexander HR. Isolated hepatic perfusion for unresectable hepatic metastases from colorectal cancer. Surgery 2001; 129: 176–87.

    Article  PubMed  CAS  Google Scholar 

  9. Desai SB, Libutti SK. Tumor angiogenesis and endothelial cell modulatory factors. J Immunother 1999; 22: 186–211.

    Article  PubMed  CAS  Google Scholar 

  10. O’Reilly MS, Holmgren L, Shing Y, et al. Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell 1994; 79: 315–28.

    Article  PubMed  Google Scholar 

  11. Westphal JR, Van’t Hullenaar R, Geurts-Moespot A, et al. Angiostatin generation by human tumor cell lines: involvement of plasminogen activators. Int J Cancer 2000 86; 760–7.

    Article  PubMed  CAS  Google Scholar 

  12. Prehn RT. Two competing influences that may explain concomitant tumor resistance. Cancer Res 1993; 53: 3266–9.

    PubMed  CAS  Google Scholar 

  13. Holmgren L, O’Reilly MS, Folkman J. Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression. Nat Med 1995; 1: 149–53.

    Article  PubMed  CAS  Google Scholar 

  14. Wen W, Moses MA, Wiedershain D, Arbiser JL, Folkman J. The generation of endostatin is mediated by elastase. Cancer Res 1999; 59: 6052–6.

    PubMed  CAS  Google Scholar 

  15. Felbor U, Dreier L, Bryant RA, Ploegh HL, Olsen BR, Mothes W. Secreted cathepsin L generates endostatin from collagen XVIII. EMBO J 2000; 19: 1187–94.

    Article  PubMed  CAS  Google Scholar 

  16. Yamagata M, Shiratori Y, Dan Y, et al. Serum endostatin levels in patients with hepatocellular carcinoma. Ann Oncol 2000; 11: 761–3.

    Article  PubMed  CAS  Google Scholar 

  17. Shweiki D, Itin A, Soffer D, Keshet E. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 1992; 359: 843–5.

    Article  PubMed  CAS  Google Scholar 

  18. Cuvier C, Jang A, Hill RP. Exposure to hypoxia, glucose starvation and acidosis: effect on invasive capacity of murine tumor cells and correlation with cathepsin (L+B) secretion. Clin Exp Metastasis 1997; 15: 19–25.

    Article  PubMed  CAS  Google Scholar 

  19. Standker L, Schrader M, Kanse SM, et al. Isolation and characterization of the circulating form of human endostatin. FEBS Lett 1997; 420: 129–33.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Surgery Branch, National Cancer Institute, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland

    Andrew L. Feldman MD, H. Richard Alexander Jr. MD, David L. Bartlett MD, Karen C. Kranda RN, Marshall S. Miller BS, Nick G. Costouros BS & Steven K. Libutti MD

  2. Diagnostic Radiology Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland

    Peter L. Choyke MD

  3. Surgery Branch, National Cancer Institute, National Institutes of Health, Building 10, Room 2B07, 9000 Rockville Pike, Bethesda, MD, 20892

    Steven K. Libutti MD

Authors
  1. Andrew L. Feldman MD
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  2. H. Richard Alexander Jr. MD
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  3. David L. Bartlett MD
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  4. Karen C. Kranda RN
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  5. Marshall S. Miller BS
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  6. Nick G. Costouros BS
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  7. Peter L. Choyke MD
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  8. Steven K. Libutti MD
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Corresponding author

Correspondence to Steven K. Libutti MD.

Additional information

Presented at the 54th Annual Meeting of the Society of Surgical Oncology, Washington, DC, from March 15–18, 2001.

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Feldman, A.L., Alexander, H.R., Bartlett, D.L. et al. A Prospective Analysis of Plasma Endostatin Levels in Colorectal Cancer Patients With Liver Metastases. Ann Surg Oncol 8, 741–745 (2001). https://doi.org/10.1007/s10434-001-0741-x

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  • DOI: https://doi.org/10.1007/s10434-001-0741-x

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