Basic Fibroblast Growth Factor Expression in Endothelial Cells: An Autocrine Role in Angiogenesis?

Abstract

bFGF belongs to the family of the heparin-binding growth factors (Basilico and Moscatelli, 1992). The single copy human bFGF gene encodes multiple bFGF isoforms with molecular weights ranging from 24 kD to 18 kD. High molecular weight isoforms (HMW-bFGFs) are colinear NH₂-terminal extensions of the better characterized 18 kD protein (Florkiewicz and Sommer, 1989). Both low and high molecular weight bFGFs exert angiogenic activity in vivo and induce cell proliferation, protease production, and Chemotaxis in cultured endothelial cells (Gualandris et al., 1994). Also, bFGF has been shown to stimulate endothelial cells to form capillary-like structures in collagen gels (Montesano et al., 1986) and to invade the amniotic membrane in vitro (Mignatti et al, 1989). The phenotype induced in vitro by bFGF in endothelial cells includes also modulation of integrin expression (Klein et al., 1993), gap-junctional intercellular communication (Pepper and Meda, 1992) and urokinase receptor upregulation (Mignatti et al., 1991). Experiments performed with neutralizing anti-bFGF antibodies have implicated endogenous bFGF in wound repair (Broadley et al., 1989), vascularization of the chorioallantoic membrane during chick embryo development (Ribatti et al., 1995), and tumor growth (Baird et al., 1986; Gross et al., 1993).