Identification of brain tumour initiating cells using the stem cell marker aldehyde dehydrogenase
Identification of brain tumour initiating cells using the stem cell marker aldehyde dehydrogenase
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DOI：
10.1016/j.ejca.2013.09.004
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发表时间：
2014-01-01
影响因子：
8.4
通讯作者：
Kim, Seung-Ki
中科院分区：
文献类型：
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作者：
Choi, Seung Ah;Lee, Ji Yeoun;Kim, Seung-Ki
乙醛脱氢酶（ALDH）已被确定在干细胞从正常和癌组织。本研究旨在评估ALDH作为适用于原发性脑肿瘤的通用脑肿瘤起始细胞（BTIC）标记物的潜力及其在维持干细胞状态中的生物学作用。来自各种原发性脑肿瘤（24例儿童和6例成人脑肿瘤）的细胞用Aldefluor染色并通过流式细胞术分选。我们研究了ALDH表达对体外BTIC特征和体内致瘤潜力的影响。原发性脑肿瘤显示ALDH的普遍表达，在各种肿瘤中有0.3-28.9%的细胞被鉴定为ALDH（+）。CD 133（+）细胞在ALDH（+）细胞中的比例高于ALDH细胞。ALDH（+）细胞产生具有高增殖潜力的神经球，表达神经干细胞标志物并分化成多种神经系统谱系。ALDH（+）细胞倾向于显示诱导多能干细胞相关基因的高表达。值得注意的是，在BTIC中通过shRNA干扰靶向敲低ALDH 1有效地干扰了它们的自我更新能力。3个月后，ALDH（+）细胞在93%的小鼠中产生肿瘤，而ALDH细胞没有。来自ALDH（+）细胞的小鼠脑肿瘤的特征性病理学与人类脑肿瘤的特征性病理学相似，并且这些细胞在体内高度增殖。我们的数据表明，原发性脑肿瘤包含具有高表达水平ALDH和BTIC特征的不同细胞亚群。ALDH可能是一个适用于原发性脑肿瘤的潜在治疗靶点。(C)2013爱思唯尔有限公司保留所有权利。
Aldehyde dehydrogenase (ALDH) has been identified in stem cells from both normal and cancerous tissues. This study aimed to evaluate the potential of ALDH as a universal brain tumour initiating cell (BTIC) marker applicable to primary brain tumours and their biological role in maintaining stem cell status.Cells from various primary brain tumours (24 paediatric and 6 adult brain tumours) were stained with Aldefluor and sorted by flow cytometry. We investigated the impact of ALDH expression on BTIC characteristics in vitro and on tumourigenic potential in vivo.Primary brain tumours showed universal expression of ALDH, with 0.3-28.9% of the cells in various tumours identified as ALDH(+). The proportion of CD133(+) cells within ALDH(+) is higher than ALDH cells. ALDH(+) cells generate neurospheres with high proliferative potential, express neural stem cell markers and differentiate into multiple nervous system lineages. ALDH(+) cells tend to show high expression of induced pluripotent stem cell-related genes. Notably, targeted knockdown of ALDH1 by shRNA interference in BTICs potently disturbed their self-renewing ability. After 3 months, ALDH(+) cells gave rise to tumours in 93% of mice whereas ALDH cells did not. The characteristic pathology of mice brain tumours from ALDH(+) cells was similar to that of human brain tumours, and these cells are highly proliferative in vivo.Our data suggest that primary brain tumours contain distinct subpopulations of cells that have high expression levels of ALDH and BTIC characteristics. ALDH might be a potential therapeutic target applicable to primary brain tumours. (C) 2013 Elsevier Ltd. All rights reserved.