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ALDH1 Is a Marker of Normal and Malignant Human Mammary Stem Cells and a Predictor of Poor Clinical Outcome
Christophe Ginestier,1 Min Hee Hur,2 Emmanuelle Charafe-Jauffret,3 Florence Monville,3 Julie Dutcher,1 Marty Brown,1 Jocelyne Jacquemier,3 Patrice Viens,3 Celina G. Kleer,1 Suling Liu,1 Anne Schott,1 Dan Hayes,1 Daniel Birnbaum,3 Max S. Wicha,1 and Gabriela Dontu1,
1 Department of Internal Medicine, Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA
2 Cheil General Hospital, Sungkyunkwan University, Seoul 100-380, South Korea
3 Laboratoire d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, UMR599 Inserm/Institut Paoli-Calmettes, Marseille 13009, France
Corresponding author
Gabriela Dontu
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.
