ANGIOGENIC PHENOTYPE INDUCED BY BASIC FIBROBLAST GROWTH-FACTOR TRANSFECTION IN BRAIN MICROVASCULAR ENDOTHELIAL-CELLS - AN IN-VITRO AUTOCRINE MODEL OF ANGIOGENESIS IN BRAIN-TUMORS

Basic fibroblast growth factor (bFGF) is expressed in the vascular end othelium of human brain tumors. To investigate the biological conseque nces of a possible autocrine modality of microvascular endothelial cel l activation by endogenous bFGF in these tumors, mouse brain microvasc ular endothelial cells were stably transfected with a retroviral expre ssion vector harboring a human bFGF cDNA. When grown on tissue culture plastic, bFGF-transfected clones show a transformed morphology and in creased saturation density. bFGF-transfectants have an invasive behavi or when seeded on three-dimensional fibrin gel and originate endotheli al cell sprouts when embedded within fibrin. Also, bFGF-transfected ce lls undergo morphogenetic organization and produce a complex network o f branching cord-like structures connecting foci of infiltrating cells when seeded on Matrigel, a laminin-rich extracellular matrix material . In contrast, parental and mock-transfected cells do not invade fibri n gels nor organize on Matrigel. These findings demonstrate that bFGF overexpression induces an angiogenic phenotype in brain microvascular endothelial cells characterized by an invasive behavior and morphogeni c potential. They support the notion that neovascularization of brain tumors can be triggered by stimuli that induce vascular endothelium to produce its own autocrine factor(s).