ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome
ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome
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DOI：
10.1016/j.stem.2007.08.014
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发表时间：
2007-11-01
期刊：
影响因子：
23.9
通讯作者：
Dontu, Gabriela
中科院分区：
文献类型：
--
作者：
Ginestier, Christophe;Hur, Min Hee;Dontu, Gabriela
由于缺乏识别和分离正常和恶性干细胞的简单方法，干细胞生物学在乳腺癌研究中的应用受到限制。利用体外和体内实验系统，我们发现醛脱氢酶活性（ALDH）增加的正常和癌症人类乳腺上皮细胞具有干/祖细胞特性。这些细胞包含正常乳腺上皮亚群，在异种移植模型中具有最广泛的谱系分化潜力和最大的生长能力。在乳腺癌中，高 ALDH 活性可识别致瘤细胞部分，其能够自我更新并产生重现亲代肿瘤异质性的肿瘤。在一系列 577 例乳腺癌中，通过免疫染色检测到的 ALDH1 表达与不良预后相关。这些发现为正常和恶性乳腺干细胞的研究提供了重要的新工具，并促进了干细胞概念的临床应用。
Application of stem cell biology to breast cancer research has been limited by the lack of simple methods for identification and isolation of normal and malignant stem cells. Utilizing in vitro and in vivo experimental systems, we show that normal and cancer human mammary epithelial cells with increased aldehyde dehydrogenase activity (ALDH) have stem/progenitor properties. These cells contain the subpopulation of normal breast epithelium with the broadest lineage differentiation potential and greatest growth capacity in a xenotransplant model. In breast carcinomas, high ALDH activity identifies the tumorigenic cell fraction, capable of self-renewal and of generating tumors that recapitulate the heterogeneity of the parental tumor. In a series of 577 breast carcinomas, expression of ALDH1 detected by immunostaining correlated with poor prognosis. These findings offer an important new tool for the study of normal and malignant breast stem cells and facilitate the clinical application of stem cell concepts.