Lumican inhibits angiogenesis by interfering with alpha2beta1 receptor activity and downregulating MMP-14 expression.
Fiche publication
Date publication
novembre 2011
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BREZILLON Stéphane
Tous les auteurs :
Niewiarowska J, Brezillon S, Sacewicz-Hofman I, Bednarek R, Maquart FX, Malinowski M, Wiktorska M, Wegrowski Y, Cierniewski CS
Lien Pubmed
Résumé
INTRODUCTION: Previous studies showed that lumican, a small leucine-rich proteoglycan that binds to alpha2 integrin I domain, is an efficient inhibitor of cell adhesion and migration. In this report, we tested its effect on angiogenesis in vitro and in vivo. MATERIALS AND METHODS: Effect of lumican on angiogenesis was evaluated by in vitro capillary tube formation test performed between Fibrin II Gels or in Matrigel and in vivo by Matrigel() plug assay in BALB/c mice. Changes in matrix metalloproteinases expression caused by lumican were analyzed in endothelial cells by real-time PCR, Western immunoblotting and gelatin zymography. RESULTS: In unchallenged endothelial cells, Matrigel induced robust capillary morphogenesis. In contrast, tube formation was dramatically reduced by lumican, and by siRNA to beta1 integrin subunit mRNA but not by control siRNA. Similarly, lumican effectively inhibited neovascularization in vivo in assays using Matrigel plugs formed in BALB/c mice. Interestingly, lumican significantly reduced expression of matrix metalloproteinases, particularly MMP-14 that is known to activate other MMPs in close vicinity of endothelial cell membranes. CONCLUSIONS: Our results provide strong evidence that lumican affects angiogenesis both by interfering with alpha2beta1 receptor activity and downregulating proteolytic activity associated with surface membranes of endothelial cells.
Référence
Thromb Res. 2011 Nov;128(5):452-7