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Blood, 1 November 2006, Vol. 108, No. 9, pp. 3035-3044. Prepublished online as a Blood First Edition Paper on July 11, 2006; DOI 10.1182/blood-2006-05-023580. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-05-023580v1 108/9/3035    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Maubant, S. Articles by Van Obberghen-Schilling, E. Search for Related Content PubMed PubMed Citation Articles by Maubant, S. Articles by Van Obberghen-Schilling, E. Related Collections Apoptosis Cell Adhesion and Motility Signal Transduction Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Blockade of v3 and v5 integrins by RGD mimetics induces anoikis and not integrin-mediated death in human endothelial cells Sylvie Maubant, Dominique Saint-Dizier, Morgane Boutillon, Francoise Perron-Sierra, Patrick J. Casara, John A. Hickman, Gordon C. Tucker, and Ellen Van Obberghen-Schilling From the Centre National de Recherche Scientifique, Unité Mixte de Recherche (CNRS UMR) 6543, Centre Antoine Lacassagne, Nice, France; and the Cancer Drug Discovery and Medicinal Chemistry Divisions, Institut de Recherches Servier, Croissy-sur-Seine, France. v integrins are thought to play an important role in tumor angiogenesis. However, discrepancies between findings with Arg-Gly-Asp (RGD) mimetics, which block angiogenesis in animal models, and knockout mice, in which loss of some v integrins enhances tumor angiogenesis, raise questions concerning the function of these integrins and the precise role of v substrate mimetics in antiangiogenic therapies. We have examined the effects of a novel non–peptide RGD mimetic, S 36578-2, on human endothelial cells to elucidate its antagonist activity and to identify possible agonist functions. S 36578-2 is highly selective for v3 and v5 integrins and induces detachment, caspase-8 activation, and apoptosis in human umbilical endothelial cells (HUVECs) plated on vitronectin. Importantly, the compound has no effect on the morphology or survival of cells plated on interstitial matrix components such as fibronectin, and it does not potentiate the apoptotic process in suspended cells. Identical results were obtained with a cyclic RGD peptide with similar target specificity. In microvascular endothelial cells, S 36578-2–induced death was also linked to its antiadhesive effect, with established lines markedly more resistant than primary cultures to the antiadhesive and proapoptotic effects. Altogether, these findings have important implications for the development of this class of antiangiogenics. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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