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J. Cell Biol.,
Volume 141, Number 7, June 29, 1998 1659-1673
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Department of Surgery, * Cardiovascular Surgery Research Laboratory and § S.A. Localio General Surgery Research
Laboratory; and 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.
Department of Cell Biology, and ¶ the Raymond and Beverly Sackler Foundation Laboratory, and the Kaplan
Cancer Center, New York University Medical Center, New York 10016
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