期刊
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
卷 1840, 期 9, 页码 2978-2987出版社
ELSEVIER
DOI: 10.1016/j.bbagen.2014.04.024
关键词
alpha 5 beta 1 integrin; alpha v beta 3/beta 5 integrin; Small antagonist; Cell adhesion; Cell migration
资金
- King Abdulaziz University KAU [HiCi/25-3-1432]
- University of Strasbourg
- Ligue Contre le Cancer (Comite du Grand Est)
- Alsace contre le Cancer
- Fondation ARC pour la Recherche sur le Cancer
- Ligue contre le Cancer
Background: Integrins are extracellular matrix receptors involved in several pathologies. Despite homologies between the RGD-binding alpha 5 beta 1 and alpha v beta 3 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 alpha 5 beta 1 and alpha v beta 3/beta 5 purified integrins. Methods: Small antagonists were either selective for alpha 5 beta 1 integrin, for alpha v beta 3/beta 5 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 alpha 5 integrin subunit were used to explore the impact of alpha 5 beta 1 integrin in the biological assays. Results: U87MG cell adhesion on fibronectin or vitronectin was respectively dependent on alpha 5 beta 1 or alpha v beta 3/beta 5 integrin. Wound healing migration was dependent on both integrins. However U87MG single cell migration was highly dependent on alpha 5 beta 1 integrin and was inhibited selectively by alpha 5 beta 1 integrin antagonists but increased by alpha v beta 3/beta 5 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 alpha 5 beta 1 integrin-dependent cell migration. (C) 2014 Elsevier B.V. All rights reserved.
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