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PMID: 18371393 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome.

Cell stem cell ·Vol. 1 ·No. 5 ·2007-11-00 ·Pages 555-67

Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, Jacquemier J, Viens P, Kleer CG, Liu S, Schott A, Hayes D, Birnbaum D, Wicha MS, Dontu G

Abstract

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.

MeSH Terms
Adult Stem Cells/enzymology,immunology Aldehyde Dehydrogenase/metabolism Aldehyde Dehydrogenase 1 Family Animals Biomarkers/analysis Breast Neoplasms/enzymology,immunology,pathology,therapy CD24 Antigen/analysis Cell Differentiation Cell Lineage Cell Proliferation Cell Separation Cells, Cultured Female Flow Cytometry Humans Hyaluronan Receptors/analysis Immunohistochemistry Isoenzymes/metabolism Mammary Glands, Human/enzymology,immunology Mice Mice, Inbred NOD Mice, SCID Neoplastic Stem Cells/enzymology,immunology,pathology Phenotype Retinal Dehydrogenase Stem Cell Transplantation Survival Analysis Tissue Array Analysis Treatment Outcome Up-Regulation Xenograft Model Antitumor Assays
Chemicals
Biomarkers CD24 Antigen CD24 protein, human CD44 protein, human Hyaluronan Receptors Isoenzymes Aldehyde Dehydrogenase 1 Family Aldehyde Dehydrogenase ALDH1A1 protein, human ALDH1A1 protein, mouse Retinal Dehydrogenase
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
Ginestier Christophe
Department of Internal Medicine, Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA.
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
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Article Info
Journal
Cell stem cell
Abbr.
Cell Stem Cell
ISSN
1934-5909
DOI
10.1016/j.stem.2007.08.014
Published
2007-11-00
Pages
555-67
Language
English
Region
United States
NLM ID
101311472
PMCID
PMC2423808
Subset
IM
Grants
NCI NIH HHS · R01 CA101860-01A1 · United States
NCI NIH HHS · R01 CA101860-04 · United States
NCI NIH HHS · CA66233 · United States
NCI NIH HHS · R01 CA101860-03 · United States
NCI NIH HHS · R01 CA101860 · United States
NCI NIH HHS · CA101860 · United States
NCI NIH HHS · 5 P 30 CA46592 · United States
NCI NIH HHS · R01 CA101860-02 · United States
Corrections
CommentIn
PMID: 18938743
CommentIn
PMID: 28575690
External Links
PubMed source DOI: 10.1016/j.stem.2007.08.014 PMC Full Text View journal details
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