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

机译:醛脱氢酶1,一种用于鉴定人鼻咽癌中癌症干细胞的功能标记

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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 +/- 0.15; 0.431 +/- 0.025 vs. 0.131 +/- 0.007; 0.121 +/- 0.126), differentiation capability and had higher migration (233.00 +/- 5.29; 228.60 +/- 9.34 vs. 123.20 +/- 7.70 vs. 97.20 +/- 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 x 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. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
机译:醛脱氢酶1(ALDH1)活性现已成功地用作各种肿瘤中的癌症干细胞(CSCs)标记。我们想调查ALDH1是否可以用作鼻咽癌(NPC)的假定CSCs标记和强大的预后因素。在这里,我们从人NPC细胞系(5-8F和CNE2)中分离了ALDH1阳性细胞,发现ALDH1阳性癌细胞生长更快,克隆形成效率更高(0.435 +/- 0.15; 0.431 +/- 0.025vs。 0.131 +/- 0.007; 0.121 +/- 0.126),分化能力和较高的迁移率(233.00 +/- 5.29; 228.60 +/- 9.34对123.20 +/- 7.70对97.20 +/- 6.61)体外阴性细胞。此外,ALDH1阳性癌细胞形成明显更多的肿瘤球。我们的体内实验表明,仅需5 x 103个ALDH1阳性NPC细胞即可诱导肿瘤。值得注意的是,ALDH1阳性细胞富含侧群(SP)细胞,干细胞样基因OCT4,BMI1,KLF4和SOX2在ALDH1阳性细胞中优先表达。免疫组织化学结果显示,ALDH1的表达与T分类(P = 0.011),N分类(P = 0.005),M分类(P = 0.002)和临床分期(P = 0.001)显着相关。有趣的是,肿瘤中ALDH1的表达与上皮-间质转化(EMT)标记显着相关,包括波形蛋白表达和E-钙黏着蛋白的丢失(分别为P = 0.003和0.008)。此外,多变量分析表明ALDH1表达是独立的预后指标(P = 0.032)。两者合计,第一次,我们证明ALDH1可能是一个新的干细胞标志物和不良生存NPC的有价值的预测指标。 (C)2012 Elsevier Ireland Ltd.保留所有权利。

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