title: Angiogenic phenotype induced by basic fibroblast growth factor transfection in brain microvascular endothelial cells.
abstract: Basic fibroblast growth factor (bFGF) is expressed in the vascular endothelium of human brain tumors. To investigate the biological consequences of a possible autocrine modality of microvascular endothelial cell activation by endogenous bFGF in these tumors, mouse brain microvascular endothelial cells were stably transfected with a retroviral expression vector harboring a human bFGF cDNA. When grown on tissue culture plastic, bFGF-transfected clones show a transformed morphology and increased saturation density. bFGF-transfectants have an invasive behavior when seeded on three-dimensional fibrin gel and originate endothelial cell sprouts when embedded within fibrin. Also, bFGF-transfected cells undergo morphogenetic organization and produce a complex network of 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 fibrin 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 morphogenic 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).
authors.affiliation: UNIV BRESCIA,DEPT BIOMED SCI & BIOTECHNOL,UNIT GEN PATHOL & IMMUNOL,I-25123 BRESCIA,ITALY. UNIV BRESCIA,DEPT BIOMED SCI & BIOTECHNOL,UNIT HISTOL,I-25123 BRESCIA,ITALY. IST NAZL RIC CANC,I-16132 GENOA,ITALY. UNIV FLORENCE,DEPT PHARMACOL,I-50134 FLORENCE,ITALY.
authors.forename: A
authors.initials: A
authors.lastname: Gualandris
authors.forename: M
authors.initials: M
authors.lastname: Rusnati
authors.forename: M
authors.initials: M
authors.lastname: Belleri
authors.forename: M
authors.initials: M
authors.lastname: Molinaritosatti
authors.forename: F
authors.initials: F
authors.lastname: Bonardi
authors.forename: A
authors.initials: A
authors.lastname: Albini
authors.forename: M
authors.initials: M
authors.lastname: Ziche
authors.forename: M
authors.initials: M
authors.lastname: Presta