Cd44+Cells Have Cancer Stem Cell-Like Properties In Nasopharyngeal Carcinoma

Background: A subpopulation of cells within a tumor appears to have the exclusive ability to initiate tumors, self-renew, and differentiate. These cancer stem cells (CSCs) are CD44+ in several epithelial malignancies. We examined the potential of CD44 to identify the CSC population in nasopharyngeal carcinoma (NPC). Methods: C666, an Epstein-Barr viruspositive (EBV+) human NPC cell line, was stained for CD44 and sorted by fluorescence-activated cell sorting (FACS). CD44+ and CD44- subpopulations were evaluated for (1) proliferative potential, (2) ability to differentiate, (3) expression of markers of epithelial-to-mesenchymal transition (EMT) and EBV genes, and (4) the ability to initiate tumors in vivo. Immunocompromised mice were injected with CD44+ and CD44- populations to assess the tumor-initiating capacity. Immunohistochemistry for CD44 was performed on an 87-patient tissue microarray (TMA), and clinical correlations were examined. Results: Heterogeneous expression of CD44 was seen among C666 cells. CD44+ cells differentiated into CD44- cells, indicating a hierarchical relationship. Further, CD44+ cells exhibited a more robust tumor-initiating capacity in the xenograft model. However, no differences were seen in proliferation rates in vitro, EBV gene expression, or expression of EMT markers between CD44+ and CD44- subsets. Patient tumors were heterogeneous for CD44 staining, and a trend toward an association between CD44 expression and clinical outcome was observed. Conclusion: NPC contains a CD44+ subpopulation with features consistent with CSCs. There was a trend toward an association between CD44 expression within NPC tumors and decreased time to local failure/relapse in patients. (c) 2012 ARSAAOA, LLC.