Expression of Integrin {alpha}6{beta}1 Enhances Tumorigenesis in Glioma Cells

摘要

The integrin 6β1 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 6 integrin subunit in the U87 cell line via retroviral-mediated gene transfer. We show that cell surface expression of the 6β1 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 6β1-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 6β1 integrin expression and may also be related to changes in the balance between cell proliferation and survival. Indeed, expression of 6β1 enhanced proliferation and decreased apoptosis of U87 cells both in the tumor and in vitro. Additionally, we demonstrate that 6β1 is implicated in glioblastoma cell migration and invasion and that laminin-111 might mediate dissemination of 6β1-positive cells in vivo. Our results highlight for the first time the considerable role of the integrin 6β1 in glioma progression.