Expression of integrin alpha6beta1 enhances tumorigenesis in glioma cells.

The integrin alpha6beta1 and its main ligand laminin-111 are overexpressed in glioblastoma, as compared with normal brain tissue, suggesting they may be involved in glioblastoma malignancy. To address this question, we stably expressed the alpha6 integrin subunit in the U87 cell line via retroviral-mediated gene transfer. We show that cell surface expression of the alpha6beta1 integrin led to dramatic changes in tumor U87 cell behavior, both in vitro and in vivo. Nude mice receiving either subcutaneous or intracerebral inoculation of alpha6beta1-expressing cells developed substantially more voluminous tumors than mice injected with control cells. The difference in tumor growth was associated with a marked increase in vascularization in response to alpha6beta1 integrin expression and may also be related to changes in the balance between cell proliferation and survival. Indeed, expression of alpha6beta1 enhanced proliferation and decreased apoptosis of U87 cells both in the tumor and in vitro. Additionally, we demonstrate that alpha6beta1 is implicated in glioblastoma cell migration and invasion and that laminin-111 might mediate dissemination of alpha6beta1-positive cells in vivo. Our results highlight for the first time the considerable role of the integrin alpha6beta1 in glioma progression.