AI Article Synopsis

  • - The study reevaluates the biological features of epithelioid malignant peritoneal mesothelioma (E-MpM) by exploring the implications of epithelial mesenchymal transition (EMT) and the potential for mesenchymal-epithelial reverse transition (MErT), alongside epigenetic changes.
  • - Analysis of surgical specimens revealed critical findings: EZH2 expression in MpM, notable c-MYC and miRNA 17-5p in E-MpM, and the influence of EMT regulators on the evolution to sarcomatoid MpM, highlighting its complex biology.
  • - Cell culture experiments reinforced that E-MpM cells exhibit stem-like characteristics and adaptability, suggesting EZH2

Article Abstract

The aim of this study was to reconsider the biological characteristics of epithelioid malignant peritoneal mesothelioma (E-MpM) in the light of new concepts about epithelial mesenchymal transition and mesenchymal epithelial reverse transition (EMT/MErT) and the role of epigenetic reprogramming in this context. To this end we profiled surgical specimens and derived cells cultures by a number of complementary approaches i.e. immunohistochemistry, immunofluorescence, in situ hybridization, biochemistry, pluripotent stem cell arrays, treatments with cytokines, growth factors and specific inhibitors.The analyses of the surgical specimens showed that i) EZH2 is expressed throughout the spectrum of MpM, ii) that E-MpM (including the high-grade undifferentiated form) are characterised by c-MYC and miRNA 17-5p expression, and iii) that progression to sarcomatoid MpM is dictated by EMT regulators. They also showed that E-MpM expressed c-MET and are enriched in E- and P-cadherins- and VEGFR2-expressing CSCs, thus strongly supporting a role for MErT reprogramming in endowing E-MpM tumour cells with stemness and plasticity, and hence with a drug resistant phenotype. The cell culture-based experiments confirmed the stemness traits and plasticity of E-MpM, and support the view that EZH2 is a druggable target in this tumor.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342756PMC
http://dx.doi.org/10.18632/oncotarget.12262DOI Listing

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