Oct‐3/4 promotes migration and invasion of glioblastoma cells

As a result of increased glioblastoma migration and invasion into normal brain parenchyma, treatment of local tumor recurrence following initial treatment in glioblastoma patients remains challenging. Recent studies have demonstrated increased Oct‐3/4 expression, a self‐renewal regulator in stem cells, in glioblastomas. However, little is known regarding the influence of Oct‐3/4 in glioblastoma cell invasiveness. The present study established Oct‐3/4‐overexpressing glioblastoma cells, which were prepared from human glioblastoma patients, to assess migration, invasion, and mRNA expression profiles of integrins and matrix metalloproteinases (MMPs). Compared with control cells, Oct‐3/4 expressing‐glioblastoma cells exhibited increased migration and invasion in wound healing and Matrigel invasion assays. Oct‐3/4 overexpression resulted in upregulated FAK and c‐Src expression, which mediate integrin signals. Vinculin accumulated along the leading edges of Oct‐3/4 expressing‐glioblastoma cells and associated with membrane ruffles during cell migration. Oct‐3/4 expressing‐cells exhibited increased MMP‐13 mRNA expression and MMP‐13 knockdown by shRNA suppressed cell invasion into Matrigel and organotypic brain slices. These results suggested that Oct‐3/4 enhanced degradation of surrounding extracellular matrix by increasing MMP‐13 expression and altering integrin signaling. Therefore, Oct‐3/4 might contribute to tumor promoting activity in glioblastomas. J. Cell. Biochem. 113: 508–517, 2012. © 2011 Wiley Periodicals, Inc.

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