title: Fibroblast growth factor-2 (FGF-2) induces vascular endothelial growth factor (VEGF) expression in the endothelial cells of forming capillaries: an autocrine mechanism contributing to angiogenesis.
abstract: FGF-2 and VEGF are potent angiogenesis inducers in vivo and in vitro. Here we show that FGF-2 induces VEGF expression in vascular endothelial cells through autocrine and paracrine mechanisms. Addition of recombinant FGF-2 to cultured endothelial cells or upregulation of endogenous FGF-2 results in increased VEGF expression. Neutralizing monoclonal antibody to VEGF inhibits FGF-2-induced endothelial cell proliferation. Endogenous 18-kD FGF-2 production upregulates VEGF expression through extracellular interaction with cell membrane receptors; high-Mr FGF-2 (22-24-kD) acts via intracellular mechanism(s). During angiogenesis induced by FGF-2 in the mouse cornea, the endothelial cells of forming capillaries express VEGF mRNA and protein. Systemic administration of neutralizing VEGF antibody dramatically reduces FGF-2-induced angiogenesis. Because occasional fibroblasts or other cell types present in the corneal stroma show no significant expression of VEGF mRNA, these findings demonstrate that endothelial cell-derived VEGF is an important autocrine mediator of FGF-2-induced angiogenesis. Thus, angiogenesis in vivo can be modulated by a novel mechanism that involves the autocrine action of vascular endothelial cell-derived FGF-2 and VEGF.
authors.affiliation: Department of Surgery, and the Kaplan Cancer Center, New York University Medical Center, New York 10016, USA.
authors.forename: G
authors.initials: G
authors.lastname: Seghezzi
authors.forename: S
authors.initials: S
authors.lastname: Patel
authors.forename: C J
authors.initials: CJ
authors.lastname: Ren
authors.forename: A
authors.initials: A
authors.lastname: Gualandris
authors.forename: G
authors.initials: G
authors.lastname: Pintucci
authors.forename: E S
authors.initials: ES
authors.lastname: Robbins
authors.forename: R L
authors.initials: RL
authors.lastname: Shapiro
authors.forename: A C
authors.initials: AC
authors.lastname: Galloway
authors.forename: D B
authors.initials: DB
authors.lastname: Rifkin
authors.forename: P
authors.initials: P
authors.lastname: Mignatti
mesh_terms: D016475:3T3 Cells; D000818:Animals; D019898:Autocrine Communication / Q000502:physiology*; D002196:Capillaries / Q000502:physiology; D002417:Cattle; D002455:Cell Division; D002478:Cells, Cultured; D016228:Endothelial Growth Factors / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008222:Lymphokines / Q000378:metabolism*; D051379:Mice; D018919:Neovascularization, Physiologic / Q000502:physiology*; D019899:Paracrine Communication / Q000502:physiology; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D008222:Lymphokines; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2