title: Effects of matrix stiffness on epithelial to mesenchymal transition-like processes of endometrial epithelial cells: Implications for the pathogenesis of endometriosis.
abstract: Endometriosis is defined as the presence of endometrial glands and stroma within extrauterine sites. Our previous study revealed an epithelial to mesenchymal transition (EMT)-like process in red peritoneal endometriosis, whereas membrane localization of E-cadherin was well maintained in epithelial cells of deep infiltrating endometriosis (DIE). Here we show that endometrial epithelial cells (EEE) grown on polyacrylamide gel substrates (PGS) of 2 kilopascal (kPa), a soft matrix, initiate a partial EMT-like process with transforming growth factor-β1 (TGF-β1) stimulation. Increasing matrix stiffness with TGF-β1 stimulation reduced the number of cell-cell contacts. Cells that retained cell-cell contacts showed decreased expression of E-cadherin and zonula occludens 1 (ZO-1) to cell-cell junctions. Few deep endometriotic epithelial cells (DEE) grown on 30-kPa PGS, which may mimic in vivo tissue compliance of DIE, retained localization of E-cadherin to cell-cell junctions with TGF-β1 treatment. Immunohistochemical analysis showed no phosphorylated Smad 2/3 nuclear localization in E-cadherin+ epithelial cells of DIE. We hypothesize that EEE may undergo an EMT-like process after attachment of endometrium to peritoneum in a TGF-β1-rich microenvironment. However, TGF-β1 signaling may be absent in DIE, resulting in a more epithelial cell-like phenotype in a rigid microenvironment.
authors.affiliation: CHU Clermont-Ferrand, CHU Estaing, Chirurgie Gynécologique, Clermont-Ferrand, France.|Clermont Université, Université d'Auvergne, ISIT UMR6284, Clermont-Ferrand, France.|CNRS, ISIT UMR6284, Clermont-Ferrand, France.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Matsuzaki
authors.affiliation: CHU Clermont-Ferrand, Service d'Anatomie et Cytologie Pathologiques, Clermont-Ferrand, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Darcha
authors.affiliation: CHU Clermont-Ferrand, CHU Estaing, Chirurgie Gynécologique, Clermont-Ferrand, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Pouly
authors.affiliation: CHU Clermont-Ferrand, CHU Estaing, Chirurgie Gynécologique, Clermont-Ferrand, France.|Clermont Université, Université d'Auvergne, ISIT UMR6284, Clermont-Ferrand, France.|CNRS, ISIT UMR6284, Clermont-Ferrand, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Canis
mesh_terms: D000199:Actins / Q000378:metabolism; D000328:Adult; D001696:Biomechanical Phenomena; D015820:Cadherins / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D004715:Endometriosis / Q000209:etiology* / Q000473:pathology*; D004717:Endometrium / Q000473:pathology*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D051785:Smad Proteins / Q000378:metabolism; D022502:Stress Fibers / Q000378:metabolism; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D055815:Young Adult; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D000199:Actins; D015820:Cadherins; D024042:Collagen Type I; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; D062826:Zonula Occludens-1 Protein