Extracellular vesicles released by mesenchymal-like prostate carcinoma cells modulate EMT state of recipient epithelial-like carcinoma cells through regulation of AR signaling

Ihsan Y. El-Sayed, Ahmad Daher, Damien Destouches, Virginie Firlej, Enis Kostallari, Pascale Maillé, Eric Huet, Nathaline Haidar-Ahmad, Guido Jenster, Alexandre de la Taille, Raghida Abou Merhi, Stéphane Terry, Francis Vacherot

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Extracellular vesicles released from cancer cells may play an important role in cancer progression by shuttling oncogenic information into recipient cells. However, our knowledge is still fragmentary and there remain numerous questions regarding the mechanisms at play and the functional consequences of these interactions. We have recently established a mesenchymal-like prostate cancer cell line (22Rv1/CR-1; Mes-PCa). In this study, we assessed the effects of the extracellular vesicles released by these cells on recipient androgen-dependent epithelial VCaP prostate cancer cells. Mes-PCa derived vesicles were found to promote mesenchymal features in the recipient epithelial-like prostate cancer cells. This transformation was accompanied by a modulation of androgen receptor signaling and activation of TGFβ signaling pathway. Moreover, recipient cells acquiring mesenchymal traits displayed enhanced migratory and invasive features as well as increased resistance to the androgen receptor antagonist, enzalutamide. Our results suggest a previously unappreciated role for Mes-PCa secreted vesicles in cancer promotion by transferring cell-mediated signals and promoting phenotypic changes in recipient prostate cancer cells.

Original languageEnglish (US)
Pages (from-to)100-111
Number of pages12
JournalCancer Letters
Volume410
DOIs
StatePublished - Dec 1 2017

Keywords

  • AR
  • EMT
  • Extracellular vesicles
  • Micro-RNAs
  • Prostate cancer
  • TGFβ

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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