Lin Chien-Hung, Hung Peir-Haur, Chen Yann-Jang
Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan.
Int J Mol Sci. 2013 Jun 26;14(7):13266-81. doi: 10.3390/ijms140713266.
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.
最近的研究表明,肿瘤内的癌症干细胞样细胞(CSCs)具有自我更新和分化的能力,并与侵袭性表型和治疗抗性相关。研究还将肿瘤进展与细胞内活性氧(ROS)水平的改变联系起来。在本研究中,我们在允许形成球体的条件下培养鼻咽癌(NPC)CSCs。所得的球体细胞表现出干性特性、上皮-间质转化(EMT)特征以及CSC表面标志物CD44的表达增加。我们进一步评估了这些CSCs中CD44表达与EMT标志物表达之间的关联,以及与氧化还原状态的任何相关性。我们表明,球体细胞中的EMT与CD44表达上调和ROS生成增加相关,这可能促进NPC的侵袭性。我们还在球体细胞中鉴定出CD44与EMT标志物N-钙黏蛋白的共表达,并在添加抗氧化剂N-乙酰半胱氨酸后下调了CD44表达。我们的结果表明,CD44在NPC中CSCs的EMT表型中起作用,并提示其参与EMT相关的ROS产生。这些发现可能有助于开发预防NPC复发和转移的新疗法。