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

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.

• Authors: C M Duzyj, I A Buhimschi, H Motawea, C A Laky, G Cozzini, G Zhao, E F Funai, C S Buhimschi
• Journal: Placenta (Placenta) Vol. 36 Issue 6 Pg. 645-51 (Jun 2015) ISSN: 1532-3102 [Electronic] Netherlands
• PMID: 25904157 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• Cadherins
• Keratin-7
• Membrane Proteins
• PSEN1 protein, human
• Presenilin-1
• Vimentin
• beta Catenin
• Amyloid Precursor Protein Secretases
• ADAM Proteins
• ADAM10 Protein
• ADAM10 protein, human

Topics

• ADAM Proteins (metabolism)
• ADAM10 Protein
• Amyloid Precursor Protein Secretases (metabolism)
• Cadherins (metabolism)
• Female
• Humans
• Keratin-7 (metabolism)
• Membrane Proteins (metabolism)
• Myometrium (metabolism, pathology)
• Placenta (metabolism, pathology)
• Placenta Accreta (metabolism, pathology)
• Pregnancy
• Presenilin-1 (metabolism)
• Trophoblasts (metabolism)
• Vimentin (metabolism)
• beta Catenin (metabolism)