Effect of preeclampsia on umbilical cord blood stem cells in relation to breast cancer susceptibility in the offspring.
Women born from a preeclamptic (PE) pregnancy are associated with a lower risk of breast cancer. Prenatal and early-life exposures are hypothesized to influence breast cancer susceptibility through their effect on stem cells. We examined stem cell populations in umbilical cord blood from PE pregnancies and compared with those from pregnancies without this condition. We isolated mononuclear cells from 58 PE and 197 normotensive (non-PE) umbilical cord blood samples and examined the different stem cell populations. Hematopoietic (CD34(+) and CD34(+)CD38(-)), endothelial (CD34(+)CD133(+), CD34(+)VEGFR2(+), CD133(+)VEGFR2(+) and CD34(+)CD133(+)VEGFR2(+)), and putative breast (EpCAM(+), EpCAM(+)CD49f(+), EpCAM(+)CD49f(+)CD117(+), CD49f(+)CD24(+), CD24(+)CD29(+) and CD24(+)CD29(+)CD49f(+)) stem/progenitor cell subpopulations were quantified by flow cytometry and compared between PE and non-PE samples. Hematopoietic CD34(+) cell counts were significantly lowered in PE compared with non-PE samples (P = 0.039, Kruskal-Wallis test). Levels of CD34(+)CD133(+) endothelial progenitor cells were also lower in PE samples (P = 0.032, multiple regression analysis). EpCAM(+) and EpCAM(+)CD49f(+) putative breast stem cell levels were significantly lowered in PE subjects (multiple regression analysis: P = 0.038 and 0.007, respectively). Stratifying by newborn gender, EpCAM(+) and EpCAM(+)CD49f(+) stem cells were significantly lowered in PE samples of female, but not male, newborns. Umbilical cord blood samples from pregnancies complicated by preeclampsia thus had significantly lower levels of hematopoietic, endothelial, and putative breast stem cells than non-PE controls. With a lowered breast cancer risk for offspring of a PE pregnancy, our findings provide support to the hypothesis that susceptibility to breast oncogenesis may be affected by conditions and processes during the prenatal period.
Department of Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA, Department of Obstetrics and Gynecology, Tufts Medical Center, Boston, MA 02111, USA, Division of Hematology/Oncology, Department of Medicine, University of Massachusetts Medical School and UMass Memorial Health Care, Worcester, MA 01655, USA, Department of Medical Epidemiology and Biostatistics, Karolinska Institute, SE171 77 Stockholm, Sweden, Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA and Department of Hygiene, Epidemiology, and Medical Statistics, University of Athens, 115 27 Athens, Greece.
Li
L
Qiu
Department of Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA, Department of Obstetrics and Gynecology, Tufts Medical Center, Boston, MA 02111, USA, Division of Hematology/Oncology, Department of Medicine, University of Massachusetts Medical School and UMass Memorial Health Care, Worcester, MA 01655, USA, Department of Medical Epidemiology and Biostatistics, Karolinska Institute, SE171 77 Stockholm, Sweden, Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA and Department of Hygiene, Epidemiology, and Medical Statistics, University of Athens, 115 27 Athens, Greece.
Sagano
S
Onoyama
Department of Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA, Department of Obstetrics and Gynecology, Tufts Medical Center, Boston, MA 02111, USA, Division of Hematology/Oncology, Department of Medicine, University of Massachusetts Medical School and UMass Memorial Health Care, Worcester, MA 01655, USA, Department of Medical Epidemiology and Biostatistics, Karolinska Institute, SE171 77 Stockholm, Sweden, Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA and Department of Hygiene, Epidemiology, and Medical Statistics, University of Athens, 115 27 Athens, Greece.
Hoi Pang
HP
Low
Department of Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA, Department of Obstetrics and Gynecology, Tufts Medical Center, Boston, MA 02111, USA, Division of Hematology/Oncology, Department of Medicine, University of Massachusetts Medical School and UMass Memorial Health Care, Worcester, MA 01655, USA, Department of Medical Epidemiology and Biostatistics, Karolinska Institute, SE171 77 Stockholm, Sweden, Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA and Department of Hygiene, Epidemiology, and Medical Statistics, University of Athens, 115 27 Athens, Greece.
Chien-I
CI
Chang
Department of Obstetrics and Gynecology, Tufts Medical Center, Boston, MA 02111, USA.
William C
WC
Strohsnitter
Department of Obstetrics and Gynecology, Tufts Medical Center, Boston, MA 02111, USA.
Errol R
ER
Norwitz
Division of Hematology/Oncology, Department of Medicine, University of Massachusetts Medical School and UMass Memorial Health Care, Worcester, MA 01655, USA.
Mary
M
Lopresti
Division of Hematology/Oncology, Department of Medicine, University of Massachusetts Medical School and UMass Memorial Health Care, Worcester, MA 01655, USA.
Kathryn
K
Edmiston
Department of Medical Epidemiology and Biostatistics, Karolinska Institute, SE171 77 Stockholm, Sweden.
Mats
M
Lambe
Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA and.
Dimitrios
D
Trichopoulos
Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA and Department of Hygiene, Epidemiology, and Medical Statistics, University of Athens, 115 27 Athens, Greece.
Pagona
P
Lagiou
Department of Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA, Department of Obstetrics and Gynecology, Tufts Medical Center, Boston, MA 02111, USA, Division of Hematology/Oncology, Department of Medicine, University of Massachusetts Medical School and UMass Memorial Health Care, Worcester, MA 01655, USA, Department of Medical Epidemiology and Biostatistics, Karolinska Institute, SE171 77 Stockholm, Sweden, Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA and Department of Hygiene, Epidemiology, and Medical Statistics, University of Athens, 115 27 Athens, Greece chung-cheng.hsieh@umassmed.edu.
Chung-Cheng
CC
Hsieh
D000293:Adolescent; D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D004198:Disease Susceptibility; D005260:Female; D005312:Fetal Blood / Q000166:cytology* / Q000378:metabolism; D053686:Fetal Stem Cells / Q000378:metabolism / Q000473:pathology*; D005434:Flow Cytometry; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D011225:Pre-Eclampsia / Q000503:physiopathology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
D012333:RNA, Messenger