FGF-1 BUT NOT FGF-4 SECRETED BY CARCINOMA-CELLS PROMOTES IN-VITRO ANDIN-VIVO ANGIOGENESIS AND RAPID TUMOR PROLIFERATION

The progressive growth of solid tumors is dependent on the tumor abili ty to recruit new blood vessels from the surrounding host tissues. We show here that acidic Fibroblast Growth Factor (FGF-1) produced by a r at bladder carcinoma transfected cell line (NET-II cells) is a potent inducer of angiogenesis. After injection in nude mice, NET-II cells tr ansfected with FGF-1 form rapidly growing carcinomas which are highly vascularized, whereas carcinoma cells producing a biologically active form of FGF-4 behave like non-producer cells. The vasculature of the t umors obtained with NET-II cells producing a secreted form of FGF-1 is dramatically expanded but lacking in some places a complete endotheli al lining. Conditioned medium from these cells induce formation of cap illary-like structures in vitro, whereas those of FGF-4 and non-secret ing FGF-1 producing cells failed to induce such structures. Our result s indicate that the expression of FGF-I may promote tumor growth, at l east in part, by inducing angiogenesis, and that the acquired ability of tumor cells to secrete FGF-1 but not FGF-4, may result in aberrant neovascularization of the tumor.