Vascular endothelial growth factor, interleukin 8, platelet-derived endothelial cell growth factor, and basic fibroblast growth factor promote angiogenesis and metastasis in human melanoma xenografts

Angiogenesis is a significant prognostic factor in melanoma, but the angiog enic factors controlling the neovascularization are not well defined. The p urpose of this study was to investigate whether the angiogenesis and metast asis of melanoma are promoted by vascular endothelial growth factor (VEGF), interleukin 8 (IL-8), platelet-derived endothelial cell growth factor (PD- ECGF), and/or basic fibroblast growth factor (bFGF). Cells from human melan oma lines (A-07, D-12, R-18, and U-25) transplanted to BALB/c nu/nu mice we re used as tumor models. Expression of angiogenic factors was studied by EL ISA, Western blotting, and immunohistochemistry. Angiogenesis was assessed by using an intradermal angiogenesis assay. Lung colonization and spontaneo us lung metastasis were determined after i.v, and intradermal inoculation o f tumor cells, respectively. The specific roles of VEGF, IL-8, PD-ECGF, and bFGF in tumor angiogenesis, Lung colonization, and spontaneous metastasis were assessed in mice treated with neutralizing antibody. The melanoma line s expressed multiple angiogenic factors, and each line showed a unique expr ession pattern. Multiple angiogenic factors promoted angiogenesis in the mo st angiogenic melanoma lines, whereas angiogenesis in the least angiogenic melanoma lines was possibly promoted solely by VEGF. Tumor growth, Lung col onization, and spontaneous metastasis were controlled by the rate of angiog enesis and hence by the angiogenic factors promoting the angiogenesis. Lung colonization and spontaneous metastasis In A-07 were inhibited by treatmen t with neutralizing antibody against VEGF, IL-8, PD-ECGF, or bFGF, Each of these angiogenic factors may promote metastasis in melanoma, because inhibi tion of one of them could not be compensated for by the others. Our observa tions suggest that efficient antiangiogenic treatment of melanoma may requi re identification and blocking of common functional features of several ang iogenic factors.