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MBC in Press, published online ahead of print June 4, 2004
Mol. Biol. Cell 10.1091/mbc.E04-03-0236

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Submitted on March 19, 2004
Revised on May 22, 2004
Accepted on May 27, 2004

NG2 Proteoglycan Promotes Endothelial Cell Motility and Angiogenesis via Engagement of Galectin-3 and {alpha}3{beta}1 Integrin

Jun-ichi Fukushi*, Irwan T. Makagiansar, and William B. Stallcup

The Burnham Institute, La Jolla, California 92037

Monitoring Editor: Martin A. Schwartz

The NG2 proteoglycan is expressed by microvascular pericytes in newly formed blood vessels. We have used in vitro and in vivo models to investigate the role of NG2 in cross-talk between pericytes and endothelial cells (EC). Binding of soluble NG2 to the EC surface induces cell motility and multicellular network formation in vitro and stimulates corneal angiogenesis in vivo. Biochemical data demonstrate the involvement of both galectin-3 and {alpha}3{beta}1 integrin in the EC response to NG2, and show that NG2, galectin-3, and {alpha}3{beta}1 form a complex on the cell surface. Transmembrane signaling via {alpha}3{beta}1 is responsible for EC motility and morphogenesis in this system. Galectin-3-dependent oligomerization may potentiate NG2-mediated activation of {alpha}3{beta}1. In conjunction with recent studies demonstrating the early involvement of pericytes in angiogenesis, these data suggest that pericyte-derived NG2 is an important factor in promoting EC migration and morphogenesis during the early stages of neovascularization.

*Corresponding author. E-mail: fukushi{at}burnham.org




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