VEGF, BFGF AND EGF IN THE ANGIOGENESIS OF HUMAN-MELANOMA XENOGRAFTS

Vascular endothelial growth factor (VEGF) is a major inducer of angiog enesis in tumors. Basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) have both been shown to interact with VEGF. The in volvement of VEGF, bFGF and EGF in melanoma angiogenesis was investiga ted here. Four human melanoma cell lines (A-07, D-12, R-18, U-25) were included in the study. Angiogenesis was quantified by scoring of tumo r oriented capillaries following intradermal cell inoculation in BALB/ c nu/nu mice. VEGF, bFGF and EGF expression and secretion we!re invest igated by Western blotting and enzyme-linked immunosorbent assay, resp ectively. Immunohistochemistry of xenografts grown intradermally was u sed to reveal VEGF and bFGF localization in vivo. The rate of angiogen esis differed substantially among the melanoma lines; the sequence fro m a high to low rate of angiogenesis was: A-07, D-12, R-18, U-25. A-07 , which induced the highest rate of angiogenesis, showed a higher rate of VEGF secretion, stronger VEGF staining by immunohistochemistry and higher bFGF expression than the other lines. U-25, which induced the lowest rate of angiogenesis, showed a higher rate of VEGF secretion th an D-12 and R-18. A-07 was the only line that showed detectable bFGF s ecretion, and R-18 was the only line that showed detectable EGF secret ion. VEGF is probably important in the angiogenesis of melanomas, Howe ver, heterogeneity in rate of angiogenesis among melanomas cannot be a ttributed to heterogeneity in rate of secretion of VEGF, bFGF and/or E GF only. (C) 1998 Wiley-Liss, Inc.