Fibroblast growth factor receptor 1-induced differentiation of endothelial cell line established from tsA58 large T transgenic mice

Angiogenesis of capillary endothelial cells includes at least four sequential cellular responses: digestion of basement membrane, migration, proliferation, and differentiation. To study differentiation of endothelial cells, we established a brain capillary endothelial cell line from H.2KbtsA58 transgenic mice. These cells are stable at 33#{176}C and display endothelial cell-specific characters, such as expression of von Willebrand factor and binding sites for the lectin Bandeiraea simpllfolla, and uptake of acetylated-low densfty lipoprotein. We measured the effects of a panel of growth factors on cellular responses. A number of factors, such as hepatocyte growth factor, vascular endothelial growth factor, and platelet-derived growth factor (PDGF)-AA failed to induce biological responses. PDGF-BB, epidermal growth factor, and acidic and basic fibroblast growth factor (FGF) induced proliferation of the cells. Of all the factors tested, only acidic FGF and basic FGF induced differentiation of the cells, visualized as the formation of tube-like structures of cells grown in three-dimensional collagen gels. All factors were also analyzed for their effects on plasminogen activator (PA)-induction and migration of the cells. Transfected cells, expressing a chimeric receptor, composed of the extracellular part from the