Endostatin competes with bFGF for binding to heparin-like glycosaminoglycans. Academic Article uri icon

Overview

MeSH

  • Binding, Competitive
  • Cells, Cultured
  • Cloning, Molecular
  • Endothelium, Vascular
  • Humans
  • Vascular Endothelial Growth Factor A

MeSH Major

  • Endostatins
  • Fibroblast Growth Factor 2
  • Heparin

abstract

  • Endostatin is a potent inhibitor of angiogenesis and tumor growth. Here, we used human endothelial cells from lung capillaries to investigate if endostatin competes with the proangiogenic growth factors, bFGF and VEGF, for binding to costimulatory heparan sulfate molecules. Endostatin inhibited 79% and 95% of the increase in proliferation induced by bFGF and VEGF165, respectively. The stimulatory effect of VEGF165 was not affected by the presence of exogenous heparin, while that of bFGF was further enhanced in the presence of up to 0.1 microg/ml heparin. The heparin-binding protein protamine completely blocked bFGF-stimulated proliferation, while it did not affect the response to VEGF165. Simultaneous addition of endostatin and protamine led to additive effects both in inhibition of proliferation and induction of apoptosis. Although bFGF was found to bind more strongly to heparin-Sepharose than endostatin, the latter, but not the former, displaced protamine from heparin in solution, which supports the notion that endostatin can compete with bFGF for binding to heparan sulfate in vivo. Taken as a whole, our results demonstrate that there is a direct connection between the dependence of endostatin activity on heparin-like glycosaminoglycans and its ability to antagonize bFGF.

publication date

  • August 5, 2005

has subject area

  • Binding, Competitive
  • Cells, Cultured
  • Cloning, Molecular
  • Endostatins
  • Endothelium, Vascular
  • Fibroblast Growth Factor 2
  • Heparin
  • Humans
  • Vascular Endothelial Growth Factor A

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1016/j.bbrc.2005.06.011

PubMed ID

  • 15985216

Additional Document Info

start page

  • 976

end page

  • 983

volume

  • 333

number

  • 3