L Qiu1, H P Low1, C-I Chang1, W C Strohsnitter2, M Anderson3, K Edmiston3, H-O Adami4, A Ekbom5, P Hall6, P Lagiou7, D Trichopoulos8, C-C Hsieh9. 1. Department of Cancer Biology, University of Massachusetts Medical School, Worcester. 2. Department of Obstetrics and Gynecology, Tufts Medical Center, Boston. 3. Division of Hematology/Oncology, Department of Medicine, University of Massachusetts Medical School and University of Massachusetts Memorial Health Care, Worcester. 4. Department of Epidemiology, Harvard School of Public Health, Boston, USA; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm. 5. Unit of Clinical Epidemiology, Department of Medicine, Karolinska Institutet/Karolinska University Hospital, Stockholm, Sweden. 6. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm. 7. Department of Epidemiology, Harvard School of Public Health, Boston, USA; Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. 8. Department of Epidemiology, Harvard School of Public Health, Boston, USA. 9. Department of Cancer Biology, University of Massachusetts Medical School, Worcester. Electronic address: chung-cheng.hsieh@umassmed.edu.
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.
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.
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