The invasive phenotype of placenta accreta extravillous trophoblasts associates with loss of E-cadherin

C. M. Duzyj, I. A. Buhimschi, H. Motawea, C. A. Laky, G. Cozzini, G. Zhao, E. F. Funai, C. S. Buhimschi

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Introduction Epithelial-to-mesenchymal transition (EMT) is a process of molecular and phenotypic epithelial cell alteration promoting invasiveness. Loss of E-cadherin (E-CAD), a transmembrane protein involved in cell adhesion, is a marker of EMT. Proteolysis into N- and C-terminus fragments by ADAM10 and presenilin-1 (PSEN-1) generates soluble (sE-CAD) and transcriptionally active forms. We studied the protein expression patterns of E-CAD in the serum and placenta of women with histologically-confirmed over-invasive placentation. Methods The patterns of expression and levels of sE-CAD were analyzed by Western blot, immunoassay, and immunoprecipitation. Tissue immunostaining for E-CAD, cytokeratin-7 (epithelial marker), vimentin (mesenchymal marker), ADAM10, PSEN-1 and β-catenin expression were investigated in parallel. Results N-terminus cleaved 80 kDa sE-CAD fragments were present in serum of pregnant women with gestational age regulation of the circulatory levels. Women with advanced trophoblast invasion did not display circulatory levels of sE-CAD different from those of women with normal placentation. Histologically, extravillous trophoblasts (EVT) closer to the placental-myometrial interface demonstrated less E-CAD staining than those found deeper in the myometrium. These cells expressed both vimentin and cytokeratin, an additional feature of EMT. EVT of placentas with advanced invasion displayed intracellular E-CAD C-terminus immunoreactivity predominating over that of the extracellular N-terminus, a pattern consistent with preferential PSEN-1 processing. Discussion Local processing of E-CAD may be an important molecular mechanism controlling the invasive phenotype of accreta EVT.

Original languageEnglish (US)
Pages (from-to)645-651
Number of pages7
JournalPlacenta
Volume36
Issue number6
DOIs
StatePublished - Jun 1 2015

All Science Journal Classification (ASJC) codes

  • Reproductive Medicine
  • Obstetrics and Gynecology
  • Developmental Biology

Keywords

  • Accreta
  • E-cadherin
  • Invasion
  • Myometrium
  • Presenilin-1
  • Trophoblast

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