Fiche publication
Date publication
septembre 2014
Auteurs
Membres identifiés du Cancéropôle Est :
Dr CHOULIER Laurence
,
Dr DONTENWILL Monique
,
Pr LEHMANN Maxime
,
Dr MARTIN Sophie
Tous les auteurs :
Ray AM, Schaffner F, Janouskova H, Noulet F, Rognan D, Lelong-Rebel I, Choulier L, Blandin AF, Lehmann M, Martin S, Kapp T, Neubauer S, Rechenmacher F, Kessler H, Dontenwill M
Lien Pubmed
Résumé
BACKGROUND: Integrins are extracellular matrix receptors involved in several pathologies. Despite homologies between the RGD-binding alpha5beta1 and alphavbeta3 integrins, selective small antagonists for each heterodimer have been proposed. Herein, we evaluated the effects of such small antagonists in a cellular context, the U87MG cell line, which express both integrins. The aim of the study was to determine if fibronectin-binding integrin antagonists are able to impact on cell adhesion and migration in relationships with their defined affinity and selectivity for alpha5beta1 and alphavbeta3/beta5 purified integrins. METHODS: Small antagonists were either selective for alpha5beta1 integrin, for alphavbeta3/beta5 integrin or non-selective. U87MG cell adhesion was evaluated on fibronectin or vitronectin. Migration assays included wound healing recovery and single cell tracking experiments. U87MG cells stably manipulated for the expression of alpha5 integrin subunit were used to explore the impact of alpha5beta1 integrin in the biological assays. RESULTS: U87MG cell adhesion on fibronectin or vitronectin was respectively dependent on alpha5beta1 or alphavbeta3/beta5 integrin. Wound healing migration was dependent on both integrins. However U87MG single cell migration was highly dependent on alpha5beta1 integrin and was inhibited selectively by alpha5beta1 integrin antagonists but increased by alphavbeta3/beta5 integrin antagonists. CONCLUSIONS: We provide a rationale for testing new integrin ligands in a cell-based assay to characterize more directly their potential inhibitory effects on integrin cellular functions. GENERAL SIGNIFICANCE: Our data highlight a single cell tracking assay as a powerful cell-based test which may help to characterize true functional integrin antagonists that block alpha5beta1 integrin-dependent cell migration.
Référence
Biochim Biophys Acta. 2014 Sep;1840(9):2978-87
