title: Novel measurements of mammary stem cells in human umbilical cord blood as prospective predictors of breast cancer susceptibility in later life.
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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cancer Biology, University of Massachusetts Medical School, Worcester.
authors.forename: L
authors.initials: L
authors.lastname: Qiu
authors.affiliation: Department of Cancer Biology, University of Massachusetts Medical School, Worcester.
authors.forename: H P
authors.initials: HP
authors.lastname: Low
authors.affiliation: Department of Cancer Biology, University of Massachusetts Medical School, Worcester.
authors.forename: C-I
authors.initials: CI
authors.lastname: Chang
authors.affiliation: Department of Obstetrics and Gynecology, Tufts Medical Center, Boston.
authors.forename: W C
authors.initials: WC
authors.lastname: Strohsnitter
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of Massachusetts Medical School and University of Massachusetts Memorial Health Care, Worcester.
authors.forename: M
authors.initials: M
authors.lastname: Anderson
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of Massachusetts Medical School and University of Massachusetts Memorial Health Care, Worcester.
authors.forename: K
authors.initials: K
authors.lastname: Edmiston
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, USA; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm.
authors.forename: H-O
authors.initials: HO
authors.lastname: Adami
authors.affiliation: Unit of Clinical Epidemiology, Department of Medicine, Karolinska Institutet/Karolinska University Hospital, Stockholm, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Ekbom
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm.
authors.forename: P
authors.initials: P
authors.lastname: Hall
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, USA; Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece.
authors.forename: P
authors.initials: P
authors.lastname: Lagiou
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, USA.
authors.forename: D
authors.initials: D
authors.lastname: Trichopoulos
authors.affiliation: Department of Cancer Biology, University of Massachusetts Medical School, Worcester. Electronic address: chung-cheng.hsieh@umassmed.edu.
authors.forename: C-C
authors.initials: CC
authors.lastname: Hsieh
mesh_terms: D000951:Antigens, Neoplasm / Q000032:analysis / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000032:analysis*; D001940:Breast / Q000166:cytology* / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism; D051927:CD24 Antigen / Q000032:analysis / Q000096:biosynthesis; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000096:biosynthesis; D002469:Cell Separation; D004198:Disease Susceptibility; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D005312:Fetal Blood / Q000166:cytology*; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D007150:Immunohistochemistry; D039503:Integrin alpha6 / Q000032:analysis / Q000096:biosynthesis; D019012:Integrin beta1 / Q000032:analysis / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000166:cytology; D018613:Microscopy, Confocal; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D051927:CD24 Antigen; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D039503:Integrin alpha6; D019012:Integrin beta1; D019009:Proto-Oncogene Proteins c-kit