Paracrine and autocrine effects of fibroblast growth factor-4 in endothelial cells

Recombinant Fibroblast Growth Factor-4 (FGF4) and FGF2 induce extracellular signal-regulated kinase-1/2 activation and DNA synthesis in murine aortic endothelial (MAE) cells. These cells co-express the IIIc/Ig-3 loops and the novel glyccpsaminoglycan-modified Illc/Ig-2 loops isoforms of FGF receptor -2 (FGFR2). The affinity of FGP4/FGFR2 interaction is 20-30 times lower tha n that of FGF2 and is enhanced by heparin, Overexpression of FGF2 or FGF4 c DNA in MAE cells results in a transformed phenotype and increased prolifera tive capacity, more evident for FGF2 than FGF4 transfectants, Both transfec tants induce angiogenesis when applied on the top of the chick embryo chori oallantoic membrane. However, in contrast with FG2-transfected cells, FGF4 transfectants show a limited capacity to growth under anchorage-independent conditions and lack the ability to invade 3D fibrin gel and to undergo mor phogenesis in vitro. Also, they fail to induce hemangiomas when injected in to the allantoic sac of the chick embryo. In conclusion, although exogenous FGF2 and FGF4 exert a similar response in MAE cells, significant differenc es are observed in the biological behavior of FGF4 ver sus FGF2 transfectan ts, indicating that the expression of the various members of the FGF family can differently affect the behavior of endothelial cells and, possibly, of other cell types, including tumor cells.