Gliomas are the most common deadly brain tumors. Human cerebral tumors express high level of α5β1 integrins. As a potential new target, α5β1 was investigated here in two human astrocytoma cell lines, A172 and U87MG. We found that a hypersialylated β1 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 β1 integrin was only recognized by the 9EG7 anti-β1 antibody and appeared devoid of other specific antibody epitopes (12G10, TS2/16 and mAb13 shown here to be N-glycosylation sensitive). Overexpression of the β1 integrin subunit in A172 cells not only increased the hypersialylated form but also led to the appearance of a non-hypersialylated β1 form also addressed to the cell surface. Compared to wild-type A172 cells, β1-A172 cells showed increased adhesion to fibronectin and decreased sensitivity to SJ749, a non-peptidic α5β1 antagonist. In addition, β1-A172 cells exhibited increased matrix dependence for normal cell cycling. Collectively, the data add new evidence for the role of β1 glycosylation/sialylation in the regulation of integrin functions.

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