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Basic Fribroblast Growth Factor Overexpression in Endothelial Cells: An Autocrine Mechanism for Angiogenesis and Angioproliferative Diseases

  • A. Gualandris
  • M. Rusnati
  • M. Bastaki
  • M. Ziche
  • M. Presta
Part of the NATO ASI Series book series (NSSA, volume 294)

Abstract

Basic fibroblast growth factor (bFGF) is expressed in vascular endothelium during tumor neovascularization and angioproliferative diseases. The ultimate significance of this observation is poorly understood. We have investigated the biological consequences of endothelial cell activation by endogeneous bFGF in a mouse aortic endothelial cell line stably transfected with a retroviral expressionvector harboring a human bFGF cDNA. Selected clones expressing 24 kD, 22 kD, and/or 18 kD bFGF isoforms were characterized by a transformed morphology and an increased saturation density. bFGF transfectants showed invasive behavior and sprouting activity in three-dimensional fibrin gels and formed a complex network of branching cord-like structures connecting foci of infiltrating cells when seeded on laminin-rich basement membrane matrix (Matrigel). The invasive and morphogenetic behavior was prevented by anti-bFGF antibody, revealing the autocrine modality of the process. The biological consequences of this autocrine activation were investigated in vivo. bFGF-transfected cells gave rise to highly vascularized lesions resembling Kaposi’s sarcoma when injected in nude mice and induced angiogenesis in avascular rabbit cornea. Injected into the allantoic sac of the chick embryo they caused an increase in vascular density and formation of mangiomas in the choriallantoic membrane. In conclusion, bFGF-overexpressing endothelial cells acquire an angiogeneic phenotype and reclute quiescent endothelium originating angioproliferative lesions in vivo. These findings demonstrated that bFGF overexpression exerts an autocrine role for endothelial cells and support the notion that tumor neovascularization and angioproliferative diseases can be triggered by stimuli that induce vascular endothelium to produce its own autocrine factors(s).

Keywords

Vascular Endothelium Basic Fibroblast Growth Factor Vascular Density AUTOCRINE Mechanism Tumor Neovascularization 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • A. Gualandris
    • 1
  • M. Rusnati
    • 1
  • M. Bastaki
    • 1
  • M. Ziche
    • 2
  • M. Presta
    • 3
  1. 1.Unit of General Pathology and Immunology, Department of Biomedical Sciences and BiotechnologyUniversity of BresciaItaly
  2. 2.Department of PharmacologyUniversity of FlorenceItaly
  3. 3.Institute of Anatomy, Histology, and EmbryologyUniversity of BariItaly

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