Abstract 4264: CD133/prominin-1 regulates the tumorigenicity of oral squamous carcinoma cells-derived cancer initiating cells

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Background: Oral squamous carcinoma cell (OSCC) is a lethal cancer with clinical, pathological, phenotypical, and biological heterogeneity. Previously, we enriched a subpopulation of oral cancer derived cancer initiating cells (OC-CICs) by tumor sphere formation approach, and identified CD133 as a putative CICs marker. However, the function of CD133 in OC-CICs remains unclear. Herein, we determined the critical role of CD133, an important CICs marker, in the maintenance of stemness characteristics and tumorigenic phenotype in OC-TICs. Methods: First, side population (SP) assay, a methodology to identify CICs in cancer cells, was performed to characterize the existence of OC-CICs. Next, we want to evaluate the expression of CD133 in OC-CIC isolated from SP cells transcriptionally and translationally. Lentiviral-mediated stable overexpression and down-regulation of CD133 expression in OSCCs and OC-CICs was established. Consequently, we investigated the effect of CD133 down-regulation or overexpression on stemness properties and tumorigenicity of OSCCs and OC-CICs, respectively. Results: We identified that CD133 was significantly up-regulated in SP cells of OSCCs. Stable overexpression of CD133 enhanced the CICs properties in OSCCs. In opposite, down-regulation of CD133 significantly reduced the self-renewal ability, side population cells, and expression of stemness genes of OC-CICs. Additionally, down-regulation of CD133 enhanced the differentiation capability but inversely diminished “stemness” gene expression of OC-CICs. Finally, knockdown of CD133 in OSCC or OC-CICs lessened both in vitro malignant abilities including cell migration/cell invasion/anchorage independent growth and in vivo tumor growth by xenotransplantation assay. Conclusion: We showed that SP cells with CICs properties existed in OSCCs. CD133 contributes to the maintenance of stemness and tumorigenicity of OC-CICs. Silencing CD133 might be a potential therapeutic target for OSCC by eliminating CICs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4264.