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Blood, 15 April 2004, Vol. 103, No. 8, pp. 3020-3028. Prepublished online as a Blood First Edition Paper on December 11, 2003; DOI 10.1182/blood-2003-08-2968. This Article Full Text (PDF) All Versions of this Article: 2003-08-2968v1 103/8/3020    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Langlois, S. Articles by Beliveau, R. Search for Related Content PubMed PubMed Citation Articles by Langlois, S. Articles by Beliveau, R. Social Bookmarking                   What's this? Submitted September 3, 2003 Accepted December 4, 2003 Membrane type 1-matrix metalloproteinase (MT1-MMP) cooperates with sphingosine 1-phosphate to induce endothelial cell migration and morphogenic differentiation Stephanie Langlois, Denis Gingras, and Richard Beliveau* Centre de Cancerologie Charles-Bruneau, Laboratoire de Medecine Moleculaire, Hopital Ste-Justine et Universite du Quebec a Montreal, Montreal, PQ, Canada * Corresponding author; email: molmed{at}justine.umontreal.ca. Membrane type 1-matrix metalloproteinase (MT1-MMP) has been suggested to play an important role in angiogenesis but the mechanisms involved remain incompletely understood. Using an in vitro model of angiogenesis in which cell migration of bovine aortic endothelial cells (BAEC) and their morphogenic differentiation into capillary-like tubular structures on Matrigel are induced by overexpression of MT1-MMP, we show that the platelet-derived bioactive lipid sphingosine 1-phosphate (S1P) is the predominant serum factor essential for MT1-MMP-dependent migration and morphogenic differentiation activities. In the presence of S1P, MT1-MMP-dependent cell migration and morphogenic differentiation were inhibited by pertussis toxin, suggesting the involvement of Gi protein-coupled receptor mediated signaling. Accordingly, cotransfection of BAEC with MT1-MMP and a constitutively active Gi2 (Q205L) mutant increased cell migration and morphogenic differentiation while treatment of BAEC overexpressing MT1-MMP with antisense oligonucleotides directed against S1P1 and S1P3, the predominant S1P receptors, significantly inhibited both processes. These results demonstrate that MT1-MMP-induced morphogenic differentiation involves the cooperation of the enzyme with platelet-derived bioactive lipids through S1P-mediated activation of Gi-coupled S1P1 and S1P3 receptors. Given the important contribution of platelets to tumor angiogenesis, the stimulation of endothelial MT1-MMP function by S1P may thus constitute an important molecular event linking hemostasis to angiogenesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. Onguchi, K. Y. Han, J.-H. Chang, and D. T. Azar Membrane Type-1 Matrix Metalloproteinase Potentiates Basic Fibroblast Growth Factor-Induced Corneal Neovascularization Am. J. Pathol., April 1, 2009; 174(4): 1564 - 1571. [Abstract] [Full Text] [PDF] S.-C. Su, E. A. Mendoza, H.-i. Kwak, and K. J. 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[Abstract] [Full Text] [PDF] P L E M van Lent, P N Span, A W Sloetjes, T R D J Radstake, A W T van Lieshout, J J T M Heuvel, C G J Sweep, and W B van den Berg Expression and localisation of the new metalloproteinase inhibitor RECK (reversion inducing cysteine-rich protein with Kazal motifs) in inflamed synovial membranes of patients with rheumatoid arthritis Ann Rheum Dis, March 1, 2005; 64(3): 368 - 374. [Abstract] [Full Text] [PDF] L. Labrecque, C. Nyalendo, S. Langlois, Y. Durocher, C. Roghi, G. Murphy, D. Gingras, and R. Beliveau Src-mediated Tyrosine Phosphorylation of Caveolin-1 Induces Its Association with Membrane Type 1 Matrix Metalloproteinase J. Biol. Chem., December 10, 2004; 279(50): 52132 - 52140. [Abstract] [Full Text] [PDF]

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