期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 333, 期 3, 页码 976-983出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2005.06.011
关键词
endostatin; protamine; bFGF; VEGF; glycosaminoglycans; heparin; endothelial cells
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 VEGF(165), 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 mu g/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. (c) 2005 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据