Opticin exerts its anti-angiogenic activity by regulating extracellular matrix adhesiveness

Research output: Contribution to journalArticle

  • External authors:
  • Magali M. Le Goff
  • Matthew J. Sutton
  • Mark Slevins
  • Ayse Latif

Abstract

Opticin is an extracellular matrix glycoprotein that we identified associated with the collagen network of the vitreous humor of the eye. Recently, we discovered that opticin possesses anti-angiogenic activity using a murine oxygen-induced retinopathy model: here, we investigate the underlying mechanism. Using an ex vivo chick chorioallantoic membrane assay, we show that opticin inhibits angiogenesis when stimulated by a range of growth factors. We show that it suppresses capillary morphogenesis, inhibits endothelial invasion, and promotes capillary network regression in three-dimensional matrices of collagen and Matrigel™. We then show that opticin binds to collagen and thereby competitively inhibits endothelial cell interactions with collagen via α 1β 1 and α 2β 1 integrins, thereby preventing the strong adhesion that is required for proangiogenic signaling via these integrins. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.

Bibliographical metadata

Original languageEnglish
Pages (from-to)28027-28036
Number of pages9
JournalJournal of Biological Chemistry
Volume287
Issue number33
DOIs
Publication statusPublished - 10 Aug 2012