Endorepellin, a novel inhibitor of angiogenesis derived from the C terminus of perlecan

Maurizio Mongiat, Shawn M. Sweeney, James D. San Antonio, Jian Fu, Renato V. Iozzo

Research output: Contribution to journalArticlepeer-review

Abstract

Perlecan, a ubiquitous basement membrane heparan sulfate proteoglycan, plays key roles in blood vessel growth and structural integrity. We discovered that the C terminus of perlecan potently inhibited four aspects of angiogenesis: endothelial cell migration, collagen-induced endothelial tube morphogenesis, and blood vessel growth in the chorioallantoic membrane and in Matrigel plug assays. The C terminus of perlecan was active at nanomolar concentrations and blocked endothelial cell adhesion to fibronectin and type I collagen, without directly binding to either protein; henceforth we have named it "endorepellin." We also found that endothelial cells possess a significant number of high affinity (K d of 11 nM) binding sites for endorepellin and that endorepellin binds endostatin and counteracts its anti-angiogenic effects. Thus, endorepellin represents a novel anti-angiogenic product, which may retard tumor neovascularization and hence tumor growth in vivo.

Original languageEnglish
Pages (from-to)4238-4249
Number of pages12
JournalJournal of Biological Chemistry
Volume278
Issue number6
DOIs
Publication statusPublished - Feb 7 2003

ASJC Scopus subject areas

  • Biochemistry

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