Signaling via fibroblast growth factor receptor-1 is dependent on extracellular matrix in capillary endothelial cell differentiation

Differentiation of endothelial cells, i.e., formation of a vessel lumen, is a prerequisite for angiogenesis. The underlying molecular mechanisms are i ll defined. We have studied a brain capillary endothelial cell line (IBEC) established from H-2K(b)-tsA58 transgenic mice. These cells form hollow tub es in three-dimensional type I collagen gels in response to fibroblast grow th factor-2 (FGF-2). Culture of IBEC on collagen gels in the presence of FG F-S protected cells from apoptosis and allowed tube formation (i.e., differ entiation) but not growth of the cells. FGF-induced differentiation, but no t cell survival, was inhibited by treatment of the cells with an anti-beta( 1)-integrin IgG. Changes in integrin expression in the collagen-gel culture s could not be detected. Rather, cell-matrix interactions critical for endo thelial cell differentiation were created during the culture, as indicated by the gradual increase in tyrosine phosphorylation of focal adhesion kinas e in the collagen-gel cultures. Inclusion of laminin in the collagen gels l ed to FGF-2-independent formation of tube structures, but cells were not pr otected from apoptosis. These data indicate that FGF receptor-1 signal tran sduction in this cell model results in cell survival. Through mechanisms de pendent on cell-matrix interactions, possibly involving the alpha(3)beta(1) -integrin and laminin produced by the collagen-cultured IBE cells, FGF stim ulation also leads to differentiation of the cells. (C) 1990 Academic Press .