High-level β1-integrin expression in a subpopulation of highly tumorigenic oral cancer cells

The beta 1 integrin (CD29) is a putative marker for cancerous epithelial stem cells. Cancer stem cells are essential to drive tumor growth, recurrence, and metastasis. We investigated the role of beta 1-integrin expression in the development of malignant phenotypes of oral squamous cell carcinoma (OSCC). Immunostaining was used to analyze the expression levels of beta 1 integrins in different types of cell colonies and tumor spheres. The results of cell viability and migration assays with and without siRNA knockdown of beta 1-integrin expression were compared. Cells expressing beta 1 integrins were evaluated for their tumorigenicity in mice. The expression of beta 1 integrins in human specimens of oral cancers at different clinical stages was semiquantified based on immunohistochemical staining of the beta 1-integrin protein. The expression level of beta 1 integrins in Meng-1 oral epidermoid carcinoma cells (OECM-1) cells was significantly higher in holoclonal colonies and tumor spheres compared to control cells. The knockdown of beta 1-integrin expression in OECM-1 cells reduced cell proliferation, migration, and tumor sphere formation. Beta-1 integrin (+) cells were more tumorigenic in the mouse xenograft model than beta 1 integrin (-) cells. In the human specimens, the expression level of the beta 1-integrin protein positively correlated with the clinical stage. The expression of beta 1 integrin in OECM-1 cells is involved in the development of malignant phenotypes of OSCC. Inhibitors for beta 1-integrin signaling may be suitable to become target-specific therapies for OSCC.