Role of cancer stem cells related molecules in oral squamous cell carcinoma

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Oral squamous cell carcinoma (OSCC) include cellular heterogeneity, as would be expected if they arose from dysregulated stem or progenitor cells as opposed to the simple clonal expansion of a mutated cell; however, stemness molecule expression levels and distribution remain unclear. To overcome this problem, stemness molecule expressions were determined in OSCC as well as their properties and prognosis. Two chromatin regulators, Bmi-1 and Hmga2, were identified in 12 tumors region and background pair cases of OSCC by microarray. Both molecules are known to promote stem cell self-renewal by negatively regulating the expressions of Ink4a and Arf tumor suppressors. The expression levels were analyzed in 38 pair cases of OSCC by Qrt-PCR and in 91 cases of the same stage of tongue SCC. Despite a similar target, Bmi-1 protein was expressed in an early cancerous region and HMGA2 protein was expressed in a more progressed region. Likewise, Bmi1-expressing tumor had no significance with regard to overall survival (P = 0.67), while HMGA2-expressing tumors had decreased overall survival (P = 0.05). Qrt-PCR analyses also correlated with protein levels. These findings suggest that Bmi-1 is an early detection marker to distinguish cancerous from non-cancerous regions, while HMGA2 is presumed to be a tumor prognosis marker. Among our OSCC analyses, these stemness molecules expressed not so many primitive rare cells in the tumor as almost all other cells in the tumor. OSCC cells with high expression of stemness molecules should partially behave exactly like stem cells.