Detection of a hypersialylated beta1 integrin endogenously expressed in the human astrocytoma cell line A172.

Gliomas are the most common deadly brain tumors. Human cerebral tumors express high level of a5Bl integrins. As a potential new target, α5s1 was investigated here in two human astrocytoma cell lines, A172 and U87MG. We found that a hypersialylated Bl integrin was endogenously expressed in A172 cells. It forms heterodimers with α5 subunits, localizes at the cell membrane and allows adhesion to fibronectin. This form of s1 integrin was only recognized by the 9EG7 anti-s1 antibody and appeared devoid of other specific antibody epitopes (12G10, TS2/16 and mAbl3 shown here to be N-glycosylation sensitive). Overexpression of the s1 integrin subunit in A172 cells not only increased the hypersialylated form but also led to the appearance of a non-hypersialylated s1 form also addressed to the cell surface. Compared to wild-type A172 cells, s1-A172 cells showed increased adhesion to fibronectin and decreased sensitivity to SJ749, a non-peptidic α5s1 antagonist. In addition, B1-A172 cells exhibited increased matrix dependence for normal cell cycling. Collectively, the data add new evidence for the role of Bl glycosylation/sialylation in the regulation of integrin functions.