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

Cell Stem Cell. 2007 Nov;1(5):555-67. doi: 10.1016/j.stem.2007.08.014.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / enzymology*
  • Adult Stem Cells / immunology
  • Aldehyde Dehydrogenase / metabolism*
  • Aldehyde Dehydrogenase 1
  • Animals
  • Biomarkers / analysis
  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / immunology
  • Breast Neoplasms / pathology
  • Breast Neoplasms / 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*
  • Mammary Glands, Human / immunology
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Neoplastic Stem Cells / enzymology*
  • Neoplastic Stem Cells / immunology
  • Neoplastic Stem Cells / pathology
  • Phenotype
  • Retinal Dehydrogenase
  • Stem Cell Transplantation
  • Survival Analysis
  • Tissue Array Analysis
  • Treatment Outcome
  • Up-Regulation
  • Xenograft Model Antitumor Assays

Substances

  • Aldehyde Dehydrogenase 1
  • Biomarkers
  • CD24 Antigen
  • CD24 protein, human
  • CD44 protein, human
  • Hyaluronan Receptors
  • Isoenzymes
  • Aldehyde Dehydrogenase
  • ALDH1A1 protein, human
  • Aldh1 protein, mouse
  • Retinal Dehydrogenase