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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:360.)
© 2000 American Heart Association, Inc.

Vascular Biology

CD9 Participates in Endothelial Cell Migration During In Vitro Wound Repair

Presented in part at the XIVth Congress of the International Society on Thrombosis and Haemostasis, June 6–12, 1997, Florence, Italy, and published in abstract form (Thromb Haemost. 1997;[suppl]:138).

Claudine Klein-Soyer; David O. Azorsa; Jean-Pierre Cazenave; François Lanza

From INSERM U. 311, Etablissement de Transfusion Sanguine de Strasbourg (C.K.-S., J.-P.C., F.L.), Strasbourg, France, and the Laboratory of Cancer Genetics (D.O.A.), National Institutes of Health/National Human Genome Research Institute, Bethesda, Md.

Correspondence to Dr Claudine Klein-Soyer, Etablissement de Transfusion Sanguine, INSERM U.311, 10 rue Spielmann, B.P. 36, Strasbourg Cédex, France. E-mail claudine.soyer{at}etss.u-strasbg.fr

Abstract—CD9, a widely expressed membrane protein of the tetraspanin family, has been implicated in diverse functions, such as signal transduction, cell adhesion, and cell motility. We tested the effects of an anti-CD9 monoclonal antibody (ALMA.1) on the migration and proliferation of human vascular endothelial cells (ECs) during repair of an in vitro mechanical wound mimicking angiogenic processes. ALMA.1 induced dose-dependent inhibition of wound repair with a 35±1.5% decrease at 20 µg/mL. Only cell migration was affected, because the rate of proliferation of ECs at the lesion margin was not modified and because the inhibition of repair was also observed for nonproliferating irradiated ECs. Monoclonal antibodies against CD63 tetraspanin (H5C6) and control mouse IgG (MOPC-21) were inactive. CD9, one of the most abundant proteins at the surface of ECs, colocalized with ß₁ or ß₃ integrins on EC membranes in double-labeling immunofluorescence experiments with ALMA.1 and an anti-ß₁ (4B4) or anti-ß₃ (SDF.3) monoclonal antibody. Moreover, ALMA.1 and 4B4 had additive inhibitory effects on lesion repair, whereas 4B4 alone also inhibited EC proliferation. In transmembrane Boyden-type assays, ALMA.1 induced dose-dependent inhibition of EC migration toward fibronectin and vitronectin with 45±6% and 31±10% inhibition, respectively, at 100 µg/mL. 4B4 inhibited migration toward fibronectin at 10 µg/mL but had no effect in the case of vitronectin. Adhesion of ECs to immobilized anti-CD9 monoclonal antibodies induced tyrosine-phosphorylated protein levels similar to those observed during interactions with ß₁ or ß₃ integrins. These results point to the involvement of CD9 in EC adhesion and migration during lesion repair and angiogenesis, probably through cooperation with integrins. As such, CD9 is a potential target to inhibit angiogenesis in metastatic and atherosclerotic processes.

Key Words: CD9 • integrins • endothelial cells • cell migration • wound repair

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