title: The multidrug-resistance transporter ABCB5 is expressed in human placenta.
abstract: ATP-binding cassette (ABC) transporters in placenta protectively transport drugs and xenobiotics. ABCB5 [subfamily B (MDR/TAP)] is a novel ABC multidrug-resistance transporter that also mediates cell fusion, stem cell function, and vasculogenic plasticity. Immunohistochemistry and double-labeling immunofluorescence staining for ABCB5 and ABCB5/CD200, respectively, was performed on formalin-fixed, paraffin-embedded placental tissue from 5 first trimester, 5 second trimester, and 5 term pregnancies as well as 5 partial moles, and 5 complete moles. In addition, tumor cells from 5 choriocarcinoma and 5 placental site trophoblastic tumor cases were examined. ABCB5 staining was observed in villous trophoblasts in 100% (5/5) of first trimester placentas (with progressive decrease in term placentas); 100% of partial moles (5/5); and 100% of complete moles (5/5). Notably, reactivity was discretely restricted to the inner trophoblast layer, with no staining of overlying syncytiotrophoblast. Antibody specificity and localization was confirmed further by in situ hybridization. ABCB5 expression was retained in 20% of choriocarcinomas (1/5) and 40% of placental site trophoblastic tumors (2/5). Prior studies have localized expression of multidrug-resistance-1, also known as ABCB1, within the syncytiotrophoblast of early placentas, where it serves a protective function as an efflux transporter. Our results show that ABCB5 is preferentially expressed in the cytotrophoblast layer of placental villi. The expression of this novel biomarker at the maternal-fetal interface raises questions on its role in placental structure and function as well as on its potential contribution to the protective efflux provided by other P-glycoprotein transporters.
authors.affiliation: Departments of Pathology (E.R.V., C.L., Q.Z., C.P.C., G.F.M Dermatology (S.D.G., M.H.F.) Division of Genetics (N.Y.F.), Brigham and Women's Hospital Harvard Medical School (E.R.V., C.L., Q.Z., S.D.G., M.H.F., N.Y.F., C.P.C., G.F.M.) Transplantation Research Center (M.H.F., N.Y.F.), Children's Hospital, Boston Converge Diagnostic Services (D.W.K.), Peabody Department of Medicine (N.Y.F.), VA Boston Healthcare System, Jamaica Plain, Massachusetts.
authors.forename: Elgida R
authors.initials: ER
authors.lastname: Volpicelli
authors.forename: Cecilia
authors.initials: C
authors.lastname: Lezcano
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhan
authors.forename: Sasha D
authors.initials: SD
authors.lastname: Girouard
authors.forename: David W
authors.initials: DW
authors.lastname: Kindelberger
authors.forename: Markus H
authors.initials: MH
authors.lastname: Frank
authors.forename: Natasha Y
authors.initials: NY
authors.lastname: Frank
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Crum
authors.forename: George F
authors.initials: GF
authors.lastname: Murphy
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis / Q000096:biosynthesis*; D002822:Choriocarcinoma / Q000378:metabolism; D005260:Female; D006801:Humans; D006828:Hydatidiform Mole / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D014328:Trophoblastic Neoplasms / Q000378:metabolism; D014327:Trophoblasts / Q000378:metabolism; D014594:Uterine Neoplasms / Q000378:metabolism*
chemical_list: C480744:ABCB5 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1