Angiogenic phenotype induced by basic fibroblast growth factor transfection in brain microvascular endothelial cells: An in vitro autocrine model of angiogenesis in brain tumors

Anna Gualandris, Marco Rusnati, Mirella Belleri, Maria Pia Molinari-Tosatti, Fabrizio Bonardi, Adriana Albini, Marina Ziche, Marco Presta

Research output: Contribution to journalArticle

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 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).

Original languageEnglish
Pages (from-to)567-573
Number of pages7
JournalInternational Journal of Oncology
Volume8
Issue number3
Publication statusPublished - Mar 1996

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Keywords

  • Angiogenesis
  • Basic fibroblast factor
  • Brain

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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