Aldehyde dehydrogenase 1 is a tumor stem cell-associated marker in lung cancer.
Aldehyde dehydrogenase 1 is a tumor stem cell-associated marker in lung cancer.
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DOI：
10.1158/1541-7786.mcr-08-0393
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发表时间：
2009-03
期刊：
影响因子：
--
通讯作者：
Katz RL
中科院分区：
文献类型：
--
作者：
Jiang F;Qiu Q;Khanna A;Todd NW;Deepak J;Xing L;Wang H;Liu Z;Su Y;Stass SA;Katz RL
肿瘤含有少量癌症干细胞（CSC），它们负责肿瘤的维持和复发。对这些 CSC 的分析可能会为癌症患者的治疗提供有效的预后和治疗策略。我们在这里报告了使用 Aldeflor 测定和荧光激活细胞分选分析从人类肺癌细胞中鉴定 CSC。具有相对较高乙醛脱氢酶 1 (ALDH1) 活性的分离癌细胞在体外表现出 CSC 的特征，包括增殖、自我更新和分化的能力、对化疗的抵抗力以及表达 CSC 表面标志物 CD133。体内实验表明，ALDH1 阳性细胞可以产生再现亲本癌细胞异质性的肿瘤。对来自三个独立队列的肺癌患者和对照的303份临床标本的免疫组织化学分析表明，ALDH1的表达与肺部肿瘤的分期和分级呈正相关，并与早期肺癌患者的不良预后相关。因此 ALDH1 是肺肿瘤干细胞相关标记物。这些发现为肺癌干细胞的研究提供了一个重要的新工具，并为肺癌患者的治疗提供了潜在的预后因素和治疗靶点。
Tumor contains small population of cancer stem cells (CSC) that are responsible for its maintenance and relapse. Analysis of these CSCs may lead to effective prognostic and therapeutic strategies for the treatment of cancer patients. We report here the identification of CSCs from human lung cancer cells using Aldefluor assay followed by fluorescence-activated cell sorting analysis. Isolated cancer cells with relatively high aldehyde dehydrogenase 1 (ALDH1) activity display in vitro features of CSCs, including capacities for proliferation, self-renewal, and differentiation, resistance to chemotherapy, and expressing CSC surface marker CD133. In vivo experiments show that the ALDH1-positive cells could generate tumors that recapitulate the heterogeneity of the parental cancer cells. Immunohistochemical analysis of 303 clinical specimens from three independent cohorts of lung cancer patients and controls show that expression of ALDH1 is positively correlated with the stage and grade of lung tumors and related to a poor prognosis for the patients with early-stage lung cancer. ALDH1 is therefore a lung tumor stem cell-associated marker. These findings offer an important new tool for the study of lung CSCs and provide a potential prognostic factor and therapeutic target for treatment of the patients with lung cancer.