Skip to main content

Advertisement

SpringerLink
Log in

Angiogenesis and melanoma

  • Published:
Current Oncology Reports Aims and scope Submit manuscript

Abstract

Angiogenesis is a process that is central to tumor growth and survival. This process is stimulated by a variety of intrinsic growth factors such as vascular endothelial growth factor, basic and acid fibroblast growth factor, and platelet-derived endothelial growth factor, among others. The process of neo-angiogenesis has been shown to be key in the proliferation of melanoma, and primarily believed to be so in the metastatic process. Biologic markers of angiogenesis are being evaluated for correlations with prognosis and biologic behavior of the tumor. These markers may also indicate susceptibility to targeted therapy. Interruption of the tumor-sustaining process of angiogenesis has become a major focus of anticancer drug development. Promising agents are in both preclinical and clinical development. Several may prove to be clinically important.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

  1. Folkman J: What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst 1990, 82:4–6. Extensive preclinical work has demonstrated the importance of neo-angiogenesis to tumor growth and development.

    Article  PubMed  CAS  Google Scholar 

  2. Folkman J, Klagsbrun M: Angiogenic factors. Science 1987, 235:442–447.

    Article  PubMed  CAS  Google Scholar 

  3. Vlaykova T, Laurila P, Muhonen T, et al.: Prognostic value of tumour vascularity in metastatic melanoma and association of blood vessel density with vascular endothelial growth factor expression. Melanoma Res 1999, 9:59–68. Demonstration of the correlation of markers of neovascularization with biologic behavior has led to further research on inhibition of this mechanism.

    Article  PubMed  CAS  Google Scholar 

  4. Claffey KP, Brown LF, del Aguila LF, et al.: Expression of vascular permeability factor/vascular endothelial growth factor by melanoma cells increases tumor growth, angiogenesis, and experimental metastasis. Cancer Res 1996, 56:172–181. This study demonstrates the correlation of the expression of vascular growth factors with evidence of the progression of melanoma and demonstration of a paracrine mechanism.

    PubMed  CAS  Google Scholar 

  5. Potgens AJ, van Altena MC, Lubsen NH, et al.: Analysis of the tumor vasculature and metastatic behavior of xenografts of human melanoma cell lines transfected with vascular permeability factor. Am J Pathol 1996, 148:1203–1217.

    PubMed  CAS  Google Scholar 

  6. Birck A, Kirkin AF, Zeuthen J, Hou-Jensen K: Expression of basic fibroblast growth factor and vascular endothelial growth factor in primary and metastatic melanoma from the same patient. Melanoma Res 1999, 9:375–381. This study evaluated the relative activity of vascular growth factors in primary and metastatic tumors and suggests a cascade of these factors in various stages of the process of angiogenesis.

    Article  PubMed  CAS  Google Scholar 

  7. Sheidow TG, Hooper PL, Crukley C, et al.: Expression of vascular endothelial growth factor in uveal melanoma and its correlation with metastasis. Br J Ophthalmol 2000, 84:750–756.

    Article  PubMed  CAS  Google Scholar 

  8. Danielsen T, Rofstad EK: VEGF, bFGF, and EGF in the angiogenesis of human melanoma xenografts. Int J Cancer 1998, 76:836–841.

    Article  PubMed  CAS  Google Scholar 

  9. Rofstad EK: Orthotopic human melanoma xenograft model systems for studies of tumour angiogenesis, pathophysiology, treatment sensitivity and metastatic pattern. Br J Cancer 1994, 70:804–812.

    PubMed  CAS  Google Scholar 

  10. Schweigerer L, Neufeld G, Friedman J, et al.: Capillary endothelial cells express basic fibroblast growth factor, a mitogen that promotes their own growth. Nature 1987, 325:257–259.

    Article  PubMed  CAS  Google Scholar 

  11. Leung DW, Cachianes G, Kuang WJ, et al.: Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 1989, 246:1306–1309.

    Article  PubMed  CAS  Google Scholar 

  12. Rofstad EK, Halsor EF: Vascular endothelial growth factor, interleukin-8, platelet-derived endothelial growth factor, and basic fibroblast growth factor promote angiogenesis and metastasis in human melanoma xenografts. Cancer Res 2000, 60:4932–4938.

    PubMed  CAS  Google Scholar 

  13. Westphal JR, vant Hullenaar R, Peek R, et al.: Angiogenic balance in human melanoma: expression of VEGF, bFGF, IL-8, PDGF, and angiostatin in relation to vascular density of xenografts in vivo. Int J Cancer 2000, 86:768–776.

    Article  PubMed  CAS  Google Scholar 

  14. Hartmann A, Kunz M, Kostlin S, et al.: Hypoxia-induced up-regulation of angiogenin in human malignant melanoma. Cancer Res 1999, 59:1578–1583.

    PubMed  CAS  Google Scholar 

  15. Rofstad EK, Danielsen T: Hypoxia-induced metastasis of human melanoma cells: involvement of vascular endothelial growth factor-mediated angiogenesis. Br J Cancer 1999, 80:1697–1707.

    Article  PubMed  CAS  Google Scholar 

  16. Danielsen T, Roftstad EK: The constitutive level of vascular endothelial growth factor (VEGF) is more important than hypoxia-induced VEGF up-regulation in the angiogenesis of human melanoma xenografts. Br J Cancer 2000, 82:1528–1534.

    Article  PubMed  CAS  Google Scholar 

  17. Guidi AJ, Abu Jawdeh G, Berse B, et al.: Vascular permeability factor (vascular endothelial growth factor) expression and angiogenesis in cervical cancer. J Natl Cancer Inst 1995, 87:1237–1245.

    Article  PubMed  CAS  Google Scholar 

  18. Takahashi Y, Kitadai Y, Bucana CD, et al.: Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis, and proliferation of human colon cancer. Cancer Res 1995, 55:2964–2968.

    Google Scholar 

  19. Obermair A, Kucera E, Mayerhofer K, et al.: Vascular endothelial growth factor (VEGF) in human breast cancer: correlation with disease-free interval. Int J Cancer 1997, 74:455–458.

    Article  PubMed  CAS  Google Scholar 

  20. Ijland SAJ, Jager MJ, Heijdra BM, et al.: Expression of angiogenic and immunosuppressive factors by uveal melanoma cell lines. Melanoma Res 1999, 9:445–450.

    Article  PubMed  CAS  Google Scholar 

  21. Stitt AW, Simpson DA, Boocock C, et al.: Expression of vascular endothelial growth factor (VEGF) and its receptors is regulated in eyes with intra-ocular tumours. J Pathol 1998, 186:306–312.

    Article  PubMed  CAS  Google Scholar 

  22. Bayer-Garner IB, Hough Jr AJ, Smoller SR: Vascular endothelial growth factor expression in malignant melanoma: prognostic versus diagnostic usefulness. Mod Pathol 1999, 12:770–774.

    PubMed  CAS  Google Scholar 

  23. Berger R, Albelda SM, Berd D, et al.: Expression of plateletendothelial cell adhesion molecule-1 (PECAM-1) during melanoma-induced angiogenesis in vivo. J Cutan Pathol 1997, 20:399–406.

    Article  Google Scholar 

  24. Neitzel LT, Neitzel CD, Magee KL, Malafa MP: Angiogenesis correlates with metastasis in melanoma. Ann Surg Oncol 1999, 6:70–74. This study evaluates clinical biologic behavior of melanoma with markers of angiogenesis.

    Article  PubMed  CAS  Google Scholar 

  25. Gitay-Goren H, Halaban R, Neufeld G: Human melanoma cells but not normal melanocytes express vascular endothelial growth factor receptors. Biochem Biophys Res Commun 1993, 190:702–708. Malignant melanoma cells demonstrate differential expression of vascular growth factors, compared with normal melanocytes, providing evidence for a paracrine mechanism in tumor angiogenesis.

    Article  PubMed  CAS  Google Scholar 

  26. Seimeister G, Schirner M, Weindel K, et al.: Two independent mechanisms essential for tumor angiogenesis: inhibition of human melanoma xenograft growth by interfering with either the vascular endothelial growth factor receptor pathway or the Tie-2 pathway. Cancer Res 1999, 59:3185–3191.

    Google Scholar 

  27. Prewett M, Huber J, Li Y, et al.: Antivascular endothelial growth factor receptor (Fetal Liver Kinase 1) monoclonal antibody inhibits tumor angiogenesis and growth of several mouse and human tumors. Cancer Res 1999, 59:5209–5218.

    PubMed  CAS  Google Scholar 

  28. Shalaby R, Rossant J, Yamaguchi TP, et al.: Failure of bloodisland formation and vasculogenesis in FLk-1-deficient mice. Nature 1995, 376:62–66.

    Article  PubMed  CAS  Google Scholar 

  29. Suri C, Jones PF, Patan S, et al.: Requisite role of angiopoietin-1, a ligand for the TIE-2 receptor, during embryonic angiogenesis. Cell 1996, 87:1171–1180.

    Article  PubMed  CAS  Google Scholar 

  30. Millauer B, Longhi MP, Plate KH, et al.: Dominant-negative inhibition of FLk-1 suppresses the growth of many tumor types in vivo. Cancer Res 1996, 56:1615–1620.

    PubMed  CAS  Google Scholar 

  31. O’Reilly MS, Holmgren L, Shing Y, et al.: A novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell 1994; 79:315–320.

    Article  PubMed  CAS  Google Scholar 

  32. Lannutti BJ, Gately ST, Quevedo ME, et al.: Human angiostatin inhibits murine hemangioendothelioma tumor growth in vivo. Cancer Res 1997, 57:5277–5282.

    PubMed  CAS  Google Scholar 

  33. Sim BKL, O’Reilly MS, Liang H, et al.: A recombinant human angiostatin protein inhibits experimental primary and metastatic cancer. Cancer Res 1997, 57:1329–1333.

    PubMed  CAS  Google Scholar 

  34. Lucas R, Holmgren L, Garcia I, et al.: Multiple forms of angiostatin induce apoptosis in endothelial cells. Blood 1998, 92:4730–4741.

    PubMed  CAS  Google Scholar 

  35. Stack MS, Gately S, Bafetti LM, et al.: Angiostatin inhibits endothelial and melanoma cellular invasion by blocking matrix-enhanced plasminogen activation. Biochem J 1999, 340:77–84.

    Article  PubMed  CAS  Google Scholar 

  36. Herbst RS, Hess KR, Mullani NA, et al.: A phase I clinical trial of recombinant human endostatin in patients with solid tumors: surrogate analyses to determine a biologically effective dose [abstract]. Proc Am Assoc Cancer Res 2001, 42:832. First clinical trial of endostatin, with biologic correlates to demonstrate that the effects expected in anti-angiogenesis actually do occur with the clinical use of this molecule.

    Google Scholar 

  37. Bhargava P, Marshall JL, Rizvi N, et al.: A phase I and pharmacokinetic study of TNP-470 administered weekly to patients with advanced cancer. Clin Cancer Res 1999, 5:1989–1995.

    PubMed  CAS  Google Scholar 

  38. Kusaka M, Sudo K, Fujita T, et al.: Potent anti-angiogenic action of AGM-1470: comparison to the fumagillin parent. Biochem Biophys Res Commun 1991, 174:1070–1076.

    Article  PubMed  CAS  Google Scholar 

  39. Kudelka A, Levy T, Verschraegen C, et al.: A phase I trial of TNP-470 administered to patients with advanced squamous cell carcinoma of the cervix. Clin Cancer Res 1997, 3:1502–1505.

    Google Scholar 

  40. Stadler W, Shapiro C, Sosman J, et al.: A multi-institutional study of the angiogenesis inhibitor, TNP-470 in metastatic renal cell carcinoma [abstract]. Proc ASCO 1998, 17:310A.

    Google Scholar 

  41. Huang S, Ullrich SE, Bar-Eli M: Regulation of tumor growth and metastasis by interleukin-10: the melanoma experience. J Interferon Cytokine Res 1999, 19:697–703.

    Article  PubMed  CAS  Google Scholar 

  42. Sidky Y, Borden E: Inhibition of angiogenesis by interferons: effects on tumors and lymphocyte-induced vascular responses. Cancer Res 1987, 47:5155–5161.

    PubMed  CAS  Google Scholar 

  43. Laird AD, Vajkoczy P, Shawver LK, et al.: SU6668 is a potent anti-angiogenic and antitumor agent that induces regression of established tumors. Cancer Res 2000, 60:4152–4160.

    PubMed  CAS  Google Scholar 

  44. Eisen T, Boshoff C, Mak I, et al.: Continuous low dose thalidomide: a phase II study in advanced melanoma, renal cell, ovarian and breast cancer. Br J Cancer 2000, 82:812–817.

    Article  PubMed  CAS  Google Scholar 

  45. Novik Y, Dutcher JP, Larkin M, Wiernik PH: Phase II study of thalidomide in advanced renal cell cancer [abstract]. Proc ASCO 2001, in press.

  46. Shalinsky DR, Brekken J, Zou H, et al.: Broad antitumor and antiangiogenic activities of AG3340, a potent and selective MMP inhibitor undergoing advanced oncology clinical trials. Ann N Y Acad Sci 1999, 878:236–270.

    Article  PubMed  CAS  Google Scholar 

  47. Shalinsky DR, Brekken J, Zou H, et al.: Marked antiangiogenic and antitumor efficacy of AG3340 in chemoresistant human non-small cell lung cancer tumors: single agent and combination chemotherapy studies. Clin Cancer Res 1999, 5:1905–1917.

    PubMed  CAS  Google Scholar 

  48. Usman N, Blatt LM: Nuclease-resistant synthetic ribozymes: developing a new class of therapeutics. J Clin Invest 2000, 106:1197–1202. Report on an agent with a new and quite different mechanism for inhibition of function of VEGF receptors.

    Article  PubMed  CAS  Google Scholar 

  49. Sandberg JA, Parker VP, Blanchard KS, et al.: Pharmacokinetics and tolerability of an antiangiogenic ribozyme (ANGIOZYME) in healthy volunteers. J Clin Pharmacol 2000, 40:1462–1469.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. New York Medical College, Our Lady of Mercy Cancer Center, 600 East 233rd Street, 10466, Bronx, NY, USA

    Janice P. Dutcher MD

Authors
  1. Janice P. Dutcher MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dutcher, J.P. Angiogenesis and melanoma. Curr Oncol Rep 3, 353–358 (2001). https://doi.org/10.1007/s11912-001-0089-1

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11912-001-0089-1

Keywords

Search

Navigation