Expression of Integrin α6β1 Enhances Tumorigenesis in Glioma Cells

The integrin alpha 6 beta 1 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 alpha 6 integrin subunit in the U87 cell fine via retroviral-mediated gene transfer. We show that cell surface expression of the alpha 6 beta 1 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 alpha 6 beta 1-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 alpha 6 beta 1 integrin expression and may also be related to changes in the balance between cell proliferation and survival. indeed, expression of alpha 6 beta 1 enhanced proliferation and decreased apoptosis of U87 cells both in the tumor and in vitro. Additionally, we demonstrate that alpha 6 beta 1 is implicated in glioblastoma cell migration and invasion and that laminin-111 might mediate dissemination of alpha 6 beta 1-positive cells in vivo. Our results highlight for the first time the considerable role of the integrin alpha 6 beta 1 in glioma. progression. (Am J Pathol 2009, 175:844-855; DOI: 10.2353/ajpath.2009.080920)