Novel measurements of mammary stem cells in human umbilical cord blood as prospective predictors of breast cancer susceptibility in later life

Ann Oncol. 2012 Jan;23(1):245-250. doi: 10.1093/annonc/mdr153. Epub 2011 Apr 22.

Abstract

Background: The size of the breast stem-cell pool could underlie the intrauterine roots of breast cancer. We studied whether breast stem cells exist in umbilical cord blood and if they correlate with hematopoietic stem-cell measurements that have been positively associated with perinatal risk factors for breast cancer.

Subjects and methods: We isolated mononuclear cells from umbilical cord blood of 170 singleton full-term pregnancies and determined, by reverse transcription polymerase chain reaction, the presence of genes of putative breast epithelial stem-cell/progenitor markers [including epithelial cell adhesion molecule (EpCAM), CD49f (α6-integrin), CD117 (c-kit receptor), CD24, and CD29 (β1-integrin)]. By immunocytochemistry, we colocalized protein expressions of EpCAM+CD49f+, CD49f+CD24+, and CD24+CD29+. We correlated concentrations of putative breast stem-cell/progenitor subpopulations, quantified by flow cytometry, with concentrations of hematopoietic stem cells.

Results: Mammary stem-cell phenotypes were identified in umbilical cord blood. The measured EpCAM+ subpopulation was positively correlated with concentrations of CD34+ and CD34+CD38- hematopoietic stem cells (both P=0.006). Additionally, EpCAM+CD49f+ and CD49f+CD24+ subpopulations were positively correlated to the CD34+ cells (P=0.03 and 0.008, respectively).

Conclusion: The positive association between measurable breast and hematopoietic stem cells in human umbilical cord blood suggests plausible mechanisms for a prenatal influence on breast cancer risk.

Publication types

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

MeSH terms

  • Antigens, Neoplasm / analysis
  • Antigens, Neoplasm / biosynthesis
  • Biomarkers, Tumor / analysis*
  • Breast / cytology*
  • Breast / metabolism
  • Breast Neoplasms / metabolism
  • CD24 Antigen / analysis
  • CD24 Antigen / biosynthesis
  • Cell Adhesion Molecules / analysis
  • Cell Adhesion Molecules / biosynthesis
  • Cell Separation
  • Disease Susceptibility
  • Epithelial Cell Adhesion Molecule
  • Female
  • Fetal Blood / cytology*
  • Flow Cytometry
  • Hematopoietic Stem Cells / cytology
  • Humans
  • Immunohistochemistry
  • Integrin alpha6 / analysis
  • Integrin alpha6 / biosynthesis
  • Integrin beta1 / analysis
  • Integrin beta1 / biosynthesis
  • Leukocytes, Mononuclear / cytology
  • Microscopy, Confocal
  • Proto-Oncogene Proteins c-kit / analysis
  • Proto-Oncogene Proteins c-kit / biosynthesis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stem Cells / cytology*
  • Stem Cells / metabolism

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • CD24 Antigen
  • Cell Adhesion Molecules
  • EPCAM protein, human
  • Epithelial Cell Adhesion Molecule
  • Integrin alpha6
  • Integrin beta1
  • Proto-Oncogene Proteins c-kit