Journal
THROMBOSIS RESEARCH
Volume 128, Issue 5, Pages 452-457Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.thromres.2011.06.011
Keywords
Lumican; Angiogenesis; Metalloproteinases; Integrins; Metastasis
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Funding
- Polish Ministry of Scientific Research and Higher Education [343/N-INCA/2008/0]
- Centre National de la Recherche Scientifique
- Institut National du Cancer (INCa) (ACI Canceropoles)
- University of Reims Champagne-Ardenne
- Region Champagne-Ardenne
- FEDER (Contrat Plan Etat Region)
- Ligue Nationale contre le Cancer (comite de la Marne)
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Introduction: Previous studies showed that lumican, a small leucine-rich proteoglycan that binds to alpha 2 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 (TM) and in vivo by Matrigel (TM) 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 (TM) induced robust capillary morphogenesis. In contrast, tube formation was dramatically reduced by lumican, and by siRNA to beta 1 integrin subunit mRNA but not by control siRNA. Similarly, lumican effectively inhibited neovascularization in vivo in assays using Matrigel (TM) 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 alpha 2 beta 1 receptor activity and downregulating proteolytic activity associated with surface membranes of endothelial cells. (C) 2011 Elsevier Ltd. All rights reserved.
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