Fiche publication
Date publication
juin 2006
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DONTENWILL Monique
,
Dr MARTIN Sophie
,
Dr RONDE Philippe
,
Dr MAGLOTT-ROTH Anne
,
Dr FUHRMANN Guy
Tous les auteurs :
Maglott A, Bartik P, Cosgun S, Klotz P, Ronde P, Fuhrmann G, Takeda K, Martin S, Dontenwill M
Lien Pubmed
Résumé
The potential role of alpha5beta1 integrins in cancer has recently attracted much interest. However, few alpha5beta1-selective antagonists have been developed compared with other integrins. The most specific nonpeptidic alpha5beta1 antagonist described thus far, SJ749, inhibits angiogenesis by affecting adhesion and migration of endothelial cells. We investigated the effects of SJ749 in two human astrocytoma cell lines, A172 and U87, which express different levels of alpha5beta1. SJ749 dose-dependently inhibited adhesion of both cell types on fibronectin. Application of SJ749 to spread cells led to formation of nonadherent spheroids for A172 cells but had no effect on U87 cell morphology. SJ749 also reduced proliferation of A172 cells due to a long lasting G0-G1 arrest, whereas U87 cells were only slightly affected. However, under nonadherent culture conditions (soft agar), SJ749 significantly reduced the number of colonies formed only by U87 cells. As U87 cells express more alpha5beta1 than A172 cells, we specifically examined the effect of SJ749 on A172 cells overexpressing alpha5. Treatment of alpha5-A172 cells with SJ749 decreased colony formation similarly to that observed in U87 cells. Therefore, in nonadherent conditions, the effect of SJ749 on tumor cell growth characteristics depends on the level of alpha5beta1 expression. Our study highlights the importance of alpha5beta1 as an anticancer target and shows for the first time that a small nonpeptidic alpha5beta1-specific antagonist affects proliferation of tumor cells.
Référence
Cancer Res. 2006 Jun 15;66(12):6002-7.
