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

Cancer Lett. 2017 Dec 1:410:100-111. doi: 10.1016/j.canlet.2017.09.010. Epub 2017 Sep 19.

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.

Keywords: AR; EMT; Extracellular vesicles; Micro-RNAs; Prostate cancer; TGFβ.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgen Antagonists / pharmacology
  • Antineoplastic Agents, Hormonal / pharmacology
  • Cell Line, Tumor
  • Cell Movement
  • Cell-Derived Microparticles / drug effects
  • Cell-Derived Microparticles / metabolism*
  • Cell-Derived Microparticles / pathology
  • Dose-Response Relationship, Drug
  • Drug Resistance, Neoplasm
  • Epithelial-Mesenchymal Transition* / drug effects
  • Humans
  • Male
  • Neoplasm Invasiveness
  • Neoplasms, Hormone-Dependent / drug therapy
  • Neoplasms, Hormone-Dependent / genetics
  • Neoplasms, Hormone-Dependent / metabolism*
  • Neoplasms, Hormone-Dependent / pathology
  • Phenotype
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Receptors, Androgen / drug effects
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism*
  • Signal Transduction* / drug effects
  • Time Factors
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism
  • Tumor Microenvironment

Substances

  • AR protein, human
  • Androgen Antagonists
  • Antineoplastic Agents, Hormonal
  • Receptors, Androgen
  • TGFB1 protein, human
  • Transforming Growth Factor beta1