Aldehyde dehydrogenase 1, a functional marker for identifying cancer stem cells in human nasopharyngeal carcinoma

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• 作者：Aibing Wu^a ; ^b ; ¹ ; Weiren Luo^a ; ^c ; ¹ ; Qianbing Zhang^a ; Zhixiong Yang^b ; Gong Zhang^a ; Siyi Li^c ; Kaitai Yao^a ; ^{yao.kaitai@yahoo.cn}
• 关键词：ALDH1 ; Nasopharyngeal carcinoma ; Cancer stem cell ; Epithelial&ndash ; mesenchymal transition ; Prognosis
• 刊名：Cancer Letters
• 出版年：2013
• 出版时间：28 April, 2013
• 年：2013
• 卷：330
• 期：2
• 页码：181-189
• 全文大小：2283 K

文摘

Aldehyde dehydrogenase 1 (ALDH1) activity has now been employed successfully as a cancer stem cells (CSCs) marker in various tumors. We wanted to investigate whether ALDH1 can be used as a putative CSCs marker and a powerful prognostic factor in nasopharyngeal carcinoma (NPC). Here, we isolated ALDH1-positive cells from human NPC cell lines (5-8F and CNE2) and found that ALDH1-positive cancer cells grew faster and had higher clone formation efficiency (0.435 ¡À 0.15; 0.431 ¡À 0.025 vs. 0.131 ¡À 0.007; 0.121 ¡À 0.126), differentiation capability and had higher migration (233.00 ¡À 5.29; 228.60 ¡À 9.34 vs. 123.20 ¡À 7.70 vs. 97.20 ¡À 6.61) than those of ALDH1-negative cancer cells in vitro. In addition, ALDH1- positive cancer cells formed significantly more tumor spheres. Our in vivo experiments showed that only 5 ¡Á 10³ ALDH1-positive NPC cells were required to induce tumors. Notably, ALDH1-positive cells are enriched in the side-population (SP) cells, and stem cells-like genes OCT4, BMI1, KLF4 and SOX2 are preferentially expressed in ALDH1-positive cells. Immunohistochemical results showed that the expression of ALDH1 correlated significantly with T classification (P = 0.011), N classification (P = 0.005), M classification (P = 0.002) and clinical stage (P = 0.001). Interestingly, ALDH1 expression in the tumor correlated significantly with epithelial-mesenchymal transition (EMT) markers including vimentin expression and loss of E-cadherin (P = 0.003 and 0.008, respectively). Furthermore, multivariate analyses showed that ALDH1 expression was an independent prognostic indicator (P = 0.032). Taken together, for the first time, we demonstrate that ALDH1 could be a novel stem cells marker and a valuable predictor of poor survival NPC.