Proteomic Characterization of Epithelial-Like Extracellular Vesicles in Advanced Endometrial Cancer

Javier Mariscal, Patricia Fernandez-Puente, Valentina Calamia, Alicia Abalo, Maria Santacana, Xavier Matias-Guiu, Rafael Lopez-Lopez, Antonio Gil-Moreno, Lorena Alonso-Alconada, Miguel Abal

Research output: Contribution to journalArticleResearch

8 Citations (Scopus)

Abstract

Copyright © 2018 American Chemical Society. Endometrial cancer (EC) is the most frequent gynecological cancer. Tumor dissemination affecting 20% of EC patients is characterized at the primary carcinoma by epithelial-to-mesenchymal transition (EMT) associated with myometrial infiltration. At distant sites, the interaction of circulating tumor cells (CTCs) with the microenvironment is crucial for metastatic colonization, with a participation of the extracellular vesicles (EVs). We comprehensively approached these primary and secondary sites to study the impact of tumor EVs on the metastatic efficiency of CTCs in EC. Tumor EVs in circulation reproduce the epithelial phenotype predominant in the primary carcinoma, whereas CTCs are characterized by an EMT phenotype. We modeled this EMT-related clinical scenario in the Hec1A endometrial cell line and characterized the epithelial-like EVs in circulation by SILAC proteome analysis. The identification of proteins involved in cell-cell and cell-matrix interaction and binding, together with in vitro evidence of an improved adhesion of CTC to a functionalized endothelium, suggests a contribution of the epithelial-like EVs in the homing of CTCs at metastatic sites. Accordingly, adhesion protein LGALS3BP was found to be significantly enriched in circulating EVs from a cohort of EC patients with a high risk of recurrence by targeted proteomics (multiple reaction monitoring), highlighting its potential in liquid biopsy in EC.
Original languageEnglish
Pages (from-to)1043-1053
JournalJournal of Proteome Research
Volume18
DOIs
Publication statusPublished - 1 Mar 2019

Keywords

  • Circulating tumor cells
  • Endometrial metastasis
  • EV proteomics
  • SILAC

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