TY - JOUR
T1 - Angiogenic phenotype induced by basic fibroblast growth factor transfection in brain microvascular endothelial cells
T2 - An in vitro autocrine model of angiogenesis in brain tumors
AU - Gualandris, Anna
AU - Rusnati, Marco
AU - Belleri, Mirella
AU - Molinari-Tosatti, Maria Pia
AU - Bonardi, Fabrizio
AU - Albini, Adriana
AU - Ziche, Marina
AU - Presta, Marco
PY - 1996/3
Y1 - 1996/3
N2 - 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 langiogenic 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).
AB - 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 langiogenic 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).
KW - Angiogenesis
KW - Basic fibroblast factor
KW - Brain
UR - http://www.scopus.com/inward/record.url?scp=0029988935&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029988935&partnerID=8YFLogxK
M3 - Article
AN - SCOPUS:0029988935
VL - 8
SP - 567
EP - 573
JO - International Journal of Oncology
JF - International Journal of Oncology
SN - 1019-6439
IS - 3
ER -