Bovine lactoferricin inhibits basic fibroblast growth factor- and vascular endothelial growth factor 165-induced angiogenesis by competing for heparin-like binding sites on endothelial cells

被引:69
作者
Mader, Jamie S.
Smyth, Daniel
Marshall, Jean
Hoskin, David W.
机构
[1] Dalhousie Univ, Fac Med, Dept Microbiol & Immunol, Halifax, NS B3H 1X5, Canada
[2] Dalhousie Univ, Fac Med, Dept Pathol, Halifax, NS B3H 1X5, Canada
关键词
D O I
10.2353/ajpath.2006.051229
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Angiogenesis is a complex process whereby new blood vessels form from pre-existing vasculature in response to proangiogenic factors such as basic fibroblast growth factor (bFGF) and the 165-kd isoform of vascular endothelial growth factor (VEGF(165)). Angiogenesis inhibitors show considerable potential in the treatment of cancer because angiogenesis is necessary for tumor growth beyond a few millimeters in diameter because of the tumor's need for oxygen and nutrient supply, as well as waste removal. Bovine lactoferricin. (LfcinB) is a peptide fragment of iron- and heparin-binding lactoferrin obtained from cow's milk. Here we provide in vivo and in vitro evidence that LfcinB has potent antiangiogenic activity. LfcinB strongly inhibited both bFGF- and VEGF(165)-induced angiogenesis in Matrigel plugs implanted in C57BL/6 mice. In addition, LfcinB inhibited the in vitro proliferation and migration of human umbilical vein endothelial cells (HUVECs) in response to bFGF or VEGF(165) but was not cytotoxic to HUVECs. Rather, LfcinB; complexed with heparin-like structures on the HUVEC surface that are involved in the binding of bFGF and VEGF(165) to their respective receptors, thereby preventing receptor-stimulated angiogenesis. These findings suggest that 1fcinB may have utility as an antiangiogenic agent for the treatment of human cancers.
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页码:1753 / 1766
页数:14
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