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

Objectives: The β1 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 β1-integrin expression in the development of malignant phenotypes of oral squamous cell carcinoma (OSCC). Materials and methods: Immunostaining was used to analyze the expression levels of β1 integrins in different types of cell colonies and tumor spheres. The results of cell viability and migration assays with and without siRNA knockdown of β1-integrin expression were compared. Cells expressing β1 integrins were evaluated for their tumorigenicity in mice. The expression of β1 integrins in human specimens of oral cancers at different clinical stages was semiquantified based on immunohistochemical staining of the β1-integrin protein. Results: The expression level of β1 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 β1-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 β1 integrin (-) cells. In the human specimens, the expression level of the β1-integrin protein positively correlated with the clinical stage. Conclusion: The expression of β1 integrin in OECM-1 cells is involved in the development of malignant phenotypes of OSCC. Clinical relevance: Inhibitors for β1-integrin signaling may be suitable to become target-specific therapies for OSCC.