ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome.
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.
Ginestier
Christophe
C
Department of Internal Medicine, Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA.
Hur
Min Hee
MH
Charafe-Jauffret
Emmanuelle
E
Monville
Florence
F
Dutcher
Julie
J
Brown
Marty
M
Jacquemier
Jocelyne
J
Viens
Patrice
P
Kleer
Celina G
CG
Liu
Suling
S
Schott
Anne
A
Hayes
Dan
D
Birnbaum
Daniel
D
Wicha
Max S
MS
Dontu
Gabriela
G
D053687:Adult Stem Cells / Q000201:enzymology* / Q000276:immunology; D000444:Aldehyde Dehydrogenase / Q000378:metabolism*; D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001943:Breast Neoplasms / Q000201:enzymology* / Q000276:immunology / Q000473:pathology / Q000628:therapy; D051927:CD24 Antigen / Q000032:analysis; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D002469:Cell Separation; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D042361:Mammary Glands, Human / Q000201:enzymology* / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D010641:Phenotype; D050697:Retinal Dehydrogenase; D033581:Stem Cell Transplantation; D016019:Survival Analysis; D046888:Tissue Array Analysis; D016896:Treatment Outcome; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays
D015415:Biomarkers; D051927:CD24 Antigen; C497889:CD24 protein, human; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D007527:Isoenzymes; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C510223:ALDH1A1 protein, human; C515028:ALDH1A1 protein, mouse; D050697:Retinal Dehydrogenase