Direct FGF receptor 1 activation through an anti-idiotypic strategy mimicks the biological activity of FGF-2 and inhibits the progression of the bladder carcinoma derived from NBT-II cells.
The hypothesis that tumor growth is angiogenesis-dependent has been documented by a considerable body of direct and indirect experimental data. Since the discovery of the vascular endothelial growth factor (VEGF), most attention has been focused on the VEGF system. Although fibroblast growth factors 1 and 2 (FGF-1 and FGF-2) can exert a strong angiogenic activity when they are supplied as a single pharmacological agent, their role in pathological angiogenesis in preclinical models remains controversial. To decipher the contribution of FGF receptors in various models of angiogenesis, we took advantage of the anti-idiotypic strategy to obtain circulating agonists specific for FGFR-1 and FGFR-2 (AIdF-1 and AIdF-2). They mimicked FGF-1 and FGF-2 for receptor binding, signal transduction, proliferation of endothelial cells and differentiation of the bladder carcinoma cell NBT-II which expresses FGFR-2b but not FGFR-1. The constitutive expression of FGFR-1 allowed binding of FGF-2 and AIdF-2 and inhibition of the proliferation of NBT-II cells. AIdF-1 and AIdF-2 induced angiogenesis in the corneal pocket assay. Although FGFR-1 dimerization achieved by AIdF-2 injection led to highly differentiated and smaller NBT-II tumors, no sign of reduction of tumor angiogenesis was observed, thus suggesting that endothelial cells are resistant to FGF.
Institut de Pharmacologie et Biologie Structurale, UMR CNRS 5089, 205 Route de Narbonne, Toulouse 31077, France.
Bernard
B
Malavaud
Sandrine
S
Pedron
Sylvie
S
Sordello
Catherine
C
Mazerolles
Clotilde
C
Billottet
Jean-Paul
JP
Thiery
Jacqueline
J
Jouanneau
Jean
J
Plouët
D000302:Adrenal Cortex / Q000098:blood supply; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D002196:Capillaries; D002455:Cell Division; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010766:Phosphorylation; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D014183:Transplantation, Heterologous; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology / Q000502:physiology
D000888:Antibodies, Anti-Idiotypic; D017468:Receptors, Fibroblast Growth Factor; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; C496348:FGFR1 protein, human; C496353:FGFR2 protein, human; C496349:Fgfr1 protein, mouse; C496354:Fgfr2 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2