Expression patterns of ERVWE1/Syncytin-1 and other placentally expressed human endogenous retroviruses along the malignant transformation process of hydatidiform moles. (March 2016)

• Record Type: Journal Article
• Authors: Bolze, Pierre-Adrien; Patrier, Sophie; Cheynet, Valérie; Oriol, Guy; Massardier, Jérôme; Hajri, Touria; Guillotte, Michèle; Bossus, Marc; Sanlaville, Damien; Golfier, François; Mallet, François
• Is Part Of: Placenta. Volume 39(2016:Mar.)
• Page Start: 116
• Page End: 124
• Publication Date: 2016-03
• Subjects: Choriocarcinoma -- Human endogenous retroviruses -- Gestational trophoblastic disease -- Gestational trophoblastic neoplasia -- Hydatidiform mole -- Syncytin-1; CHM complete hydatidiform mole -- DC-SIGN dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin -- GCM1 glial cell missing 1 -- GTN gestational trophoblastic neoplasia -- hASCT1 human neutral amino acid transporter 1 -- hASCT2 human neutral amino acid transporter 2 -- hCG human chorionic gonadotropin -- HELLP hemolysis or elevated liver enzymes and low platelets -- IUGR intra-uterine growth retardation -- LTR long terminal repeat -- PHM partial hydatidiform mole -- PSTT placental site trophoblastic tumor -- RE relative expression -- SU surface subunit -- TLR4 toll-like receptor 4 -- TM transmembrane subunit; Placenta -- Periodicals; Reproduction -- Periodicals; Placenta -- Periodicals; Placenta -- Périodiques; Reproduction -- Périodiques; 612.63
• DOI: 10.1016/j.placenta.2016.01.011
• Languages: English
• ISSNs: 0143-4004

Abstract

Abstract: Introduction: Up to 20% of hydatidiform moles are followed by malignant transformation in gestational trophoblastic neoplasia and require chemotherapy. Syncytin-1 is involved in human placental morphogenesis and is also expressed in various cancers. We assessed the predictive value of the expression of Syncytin-1 and its interactants in the malignant transformation process of hydatidiform moles. Methods: Syncytin-1 glycoprotein was localized by immunohistochemistry in hydatidiform moles, gestational trophoblastic neoplasia and control placentas. The transcription levels of its locus ERVWE1, its interaction partners (hASCT1, hASCT2, TLR4 and DC-SIGN) and two loci (ERVFRDE1 and ERV3) involved the expression of other placental envelopes were assessed by real-time PCR. Results: Syncytin-1 glycoprotein was expressed in syncytiotrophoblast of hydatidiform moles with an apical enhancement when compared with normal placentas. Moles with further malignant transformation had a higher staining intensity of Syncytin-1 surface unit C-terminus but the transcription level of its locus ERVWE1 was not different from that of moles with further remission and normal placentas. hASCT1 and TLR4, showed lower transcription levels in complete moles when compared to normal placentas. ERVWE1, ERVFRDE1 and ERV3 transcription was down-regulated in hydatidiform moles and gestational trophoblastic neoplasia. Conclusions: Variations of Syncytin-1 protein localization and down-regulation of hASCT1 and TLR4 transcription are likely to reflect altered functions of Syncytin-1 in the premalignant context of complete moles. The reduced transcription in gestational trophoblastic diseases of ERVWE1, ERVFRDE1 and ERV3, which expression during normal pregnancy is differentially regulated by promoter region methylation, suggest a joint dysregulation mechanism in malignant context. Highlights: Syncytin-1 glycoprotein is expressed in the syncytiotrophoblast of hydatidiform moles. Syncytin-1 interaction partners TLR4 and hASCT1 are down regulated in complete moles. Syncytin-1 surface-unit is overexpressed in moles with further malignant transformation.