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CD44 Is Associated with the Aggressive Phenotype of Nasopharyngeal Carcinoma through Redox Regulation
Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan
Department of Pediatrics, Zhongxing Branch, Taipei City Hospital, Taipei 103, Taiwan
Department of Medical Research, Ditmanson Medical Foundation Chia-yi Christian Hospital, Chia-yi 600, Taiwan
Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan
Department of Pediatrics, Renai Branch, Taipei City Hospital, Taipei 106, Taiwan
* Author to whom correspondence should be addressed.
Received: 13 May 2013; in revised form: 18 June 2013 / Accepted: 19 June 2013 / Published: 26 June 2013
Abstract: Recent studies have shown that cancer stem-like cells (CSCs) within a tumor have the capacity for self-renewal and differentiation, and are associated with an aggressive phenotype and therapeutic resistance. Studies have also associated tumor progression with alterations in the levels of intracellular reactive oxygen species (ROS). In this study, we cultured nasopharyngeal carcinoma (NPC) CSCs in conditions that allowed sphere formation. The resulting sphere cells displayed stemness properties, characteristics of the epithelial–mesenchymal transition (EMT), and increased expression of the CSC surface marker CD44. We further evaluated the association between CD44 expression and EMT marker expression, and any correlation with redox status, in these CSCs. We showed that the EMT in sphere cells is associated with the upregulation of CD44 expression and increased ROS generation, which might promote NPC aggressiveness. We also identified the coexpression of CD44 with the EMT marker N-cadherin in sphere cells, and downregulated CD44 expression after the addition of the antioxidant N-acetyl cysteine. Our results indicate that CD44 plays a role in the EMT phenotype of CSCs in NPC, and suggest its involvement in EMT-associated ROS production. These findings might facilitate the development of a novel therapy for the prevention of NPC recurrence and metastasis.
Keywords: CD44; nasopharyngeal carcinoma; cancer stem cells; epithelial-mesenchymal transition; reactive oxygen species
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MDPI and ACS Style
Lin, C.-H.; Hung, P.-H.; Chen, Y.-J. CD44 Is Associated with the Aggressive Phenotype of Nasopharyngeal Carcinoma through Redox Regulation. Int. J. Mol. Sci. 2013, 14, 13266-13281.
Lin C-H, Hung P-H, Chen Y-J. CD44 Is Associated with the Aggressive Phenotype of Nasopharyngeal Carcinoma through Redox Regulation. International Journal of Molecular Sciences. 2013; 14(7):13266-13281.
Lin, Chien-Hung; Hung, Peir-Haur; Chen, Yann-Jang. 2013. "CD44 Is Associated with the Aggressive Phenotype of Nasopharyngeal Carcinoma through Redox Regulation." Int. J. Mol. Sci. 14, no. 7: 13266-13281.