FGF-1 but not FGF-4 secreted by carcinoma cells promotes in vitro and in vivo angiogenesis and rapid tumor proliferation.
The progressive growth of solid tumors is dependent on the tumor ability to recruit new blood vessels from the surrounding host tissues. We show here that acidic Fibroblast Growth Factor (FGF-1) produced by a rat bladder carcinoma transfected cell line (NBT-II cells) is a potent inducer of angiogenesis. After injection in nude mice, NBT-II cells transfected 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 tumors obtained with NBT-II cells producing a secreted form of FGF-1 is dramatically expanded but lacking in some places a complete endothelial lining. Conditioned medium from these cells induce formation of capillary-like structures in vitro, whereas those of FGF-4 and non-secreting FGF-1 producing cells failed to induce such structures. Our results indicate that the expression of FGF-1 may promote tumor growth, at least 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.
Laboratoire de Physiopathologie du Développement, URA 1337 CNRS, Ecole Normale Superieure, Paris, France.
J
J
Jouanneau
G
G
Moens
R
R
Montesano
J P
JP
Thiery
D000818:Animals; D015153:Blotting, Western; D002277:Carcinoma / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism / Q000494:pharmacology*; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D008934:Mitogens / Q000494:pharmacology; D009389:Neovascularization, Pathologic / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D014162:Transfection / Q000235:genetics; D014407:Tumor Cells, Cultured; D014841:von Willebrand Factor / Q000276:immunology
D017077:Culture Media, Conditioned; C496446:Fgf4 protein, mouse; C496447:Fgf4 protein, rat; D051519:Fibroblast Growth Factor 4; D008934:Mitogens; D011518:Proto-Oncogene Proteins; D014841:von Willebrand Factor; D016220:Fibroblast Growth Factor 1; D005346:Fibroblast Growth Factors