Fiche publication
Date publication
mai 2008
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DONTENWILL Monique
,
Dr MARTIN Sophie
Tous les auteurs :
Bartik P, Maglott A, Entlicher G, Vestweber D, Takeda K, Martin S, Dontenwill M
Lien Pubmed
Résumé
Gliomas are the most common deadly brain tumors. Human cerebral tumors express high level of alpha 5 beta 1 integrins. As a potential new target, alpha 5 beta 1 was investigated here in two human astrocytoma cell lines, A172 and U87MG. We found that a hypersialylated beta 1 integrin was endogenously expressed in A172 cells. It forms heterodimers with alpha 5 subunits, localizes at the cell membrane and allows adhesion to fibronectin. This form of 61 integrin was only recognized by the 9EG7 anti-beta 1 antibody and appeared devoid of other specific antibody epitopes (12G10, TS2/16 and mAb13 shown here to be N-glycosylation sensitive). Overexpression of the beta 1 integrin subunit in A172 cells not only increased the hypersialylated form but also led to the appearance of a non-hypersialylated 61 form also addressed to the cell surface. Compared to wild-type A172 cells, beta 1-A172 cells showed increased adhesion to fibronectin and decreased sensitivity to SJ749, a non-peptidic alpha 5 beta 1 antagonist. In addition, beta 1-A172 cells exhibited increased matrix dependence for normal cell cycling. Collectively, the data add new evidence for the role of beta 1 glycosylation/sialylation in the regulation of integrin functions.
Référence
Int J Oncol. 2008 May;32(5):1021-31.
