title: The invasive phenotype of placenta accreta extravillous trophoblasts associates with loss of E-cadherin.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  Local processing of E-CAD may be an important molecular mechanism controlling the invasive phenotype of accreta EVT.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address: christina.duzyj@rutgers.edu.
authors.forename: C M
authors.initials: CM
authors.lastname: Duzyj
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA; Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital and Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43215, USA.
authors.forename: I A
authors.initials: IA
authors.lastname: Buhimschi
authors.affiliation: Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital and Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43215, USA.
authors.forename: H
authors.initials: H
authors.lastname: Motawea
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Laky
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: G
authors.initials: G
authors.lastname: Cozzini
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA; Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital and Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43215, USA.
authors.forename: G
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: E F
authors.initials: EF
authors.lastname: Funai
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: C S
authors.initials: CS
authors.lastname: Buhimschi
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000072197:ADAM10 Protein; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism*; D005260:Female; D006801:Humans; D053552:Keratin-7 / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D009215:Myometrium / Q000378:metabolism / Q000473:pathology; D010920:Placenta / Q000378:metabolism* / Q000473:pathology; D010921:Placenta Accreta / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D053764:Presenilin-1 / Q000378:metabolism; D014327:Trophoblasts / Q000378:metabolism*; D014746:Vimentin / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D015820:Cadherins; D053552:Keratin-7; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D014746:Vimentin; D051176:beta Catenin; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human
keywords: Accreta; E-cadherin; Invasion; Myometrium; Presenilin-1; Trophoblast