Molecular Definition of Breast Tumor Heterogeneity

Cancer Cell. 2007 Mar;11(3):259-73. doi: 10.1016/j.ccr.2007.01.013.

Abstract

Cells with distinct phenotypes including stem-cell-like properties have been proposed to exist in normal human mammary epithelium and breast carcinomas, but their detailed molecular characteristics and clinical significance are unclear. We determined gene expression and genetic profiles of cells purified from cancerous and normal breast tissue using markers previously associated with stem-cell-like properties. CD24+ and CD44+ cells from individual tumors were clonally related but not always identical. CD44+ cell-specific genes included many known stem-cell markers and correlated with decreased patient survival. The TGF-beta pathway was specifically active in CD44+ cancer cells, where its inhibition induced a more epithelial phenotype. Our data suggest prognostic relevance of CD44+ cells and therapeutic targeting of distinct tumor cell populations.

Publication types

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

MeSH terms

  • Antigens, CD / metabolism
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • CD24 Antigen / metabolism
  • Carcinoma, Ductal, Breast / genetics
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / pathology
  • Cell Lineage
  • Cells, Cultured
  • Endothelial Protein C Receptor
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hyaluronan Receptors / metabolism
  • Mammary Glands, Human / metabolism
  • Mammary Glands, Human / pathology
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Pregnancy
  • Receptors, Cell Surface / metabolism
  • Signal Transduction
  • Stem Cells / metabolism*
  • Stem Cells / pathology
  • Transforming Growth Factor beta / metabolism

Substances

  • Antigens, CD
  • Biomarkers, Tumor
  • CD24 Antigen
  • Endothelial Protein C Receptor
  • Hyaluronan Receptors
  • PROCR protein, human
  • Receptors, Cell Surface
  • Transforming Growth Factor beta