Ginestier Christophe, Hur Min Hee, Charafe-Jauffret Emmanuelle, Monville Florence, Dutcher Julie, Brown Marty, Jacquemier Jocelyne, Viens Patrice, Kleer Celina G, Liu Suling, Schott Anne, Hayes Dan, Birnbaum Daniel, Wicha Max S, Dontu Gabriela
Department of Internal Medicine, Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA.
Cell Stem Cell. 2007 Nov;1(5):555-67. doi: 10.1016/j.stem.2007.08.014.
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.
干细胞生物学在乳腺癌研究中的应用一直受到限制,因为缺乏识别和分离正常及恶性干细胞的简单方法。利用体外和体内实验系统,我们发现醛脱氢酶活性(ALDH)增强的正常和癌性人乳腺上皮细胞具有干细胞/祖细胞特性。在异种移植模型中,这些细胞包含具有最广泛谱系分化潜能和最大生长能力的正常乳腺上皮亚群。在乳腺癌中,高ALDH活性可识别致瘤细胞部分,该部分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表达与预后不良相关。这些发现为正常和恶性乳腺干细胞的研究提供了一个重要的新工具,并促进了干细胞概念的临床应用。