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Article Dans Une Revue Cell Death and Disease Année : 2017

Cell-based therapy using miR-302-367 expressing cells represses glioblastoma growth

Mohamed Fareh
  • Fonction : Auteur
Fabien Almairac
  • Fonction : Auteur
Laurent Turchi
Fanny Burel-Vandenbos
  • Fonction : Auteur
Philippe Paquis
  • Fonction : Auteur
Denys Fontaine
  • Fonction : Auteur
Sandra Lacas-Gervais
Marie-Pierre Junier
  • Fonction : Auteur
Thierry Virolle
  • Fonction : Auteur

Résumé

Glioblastomas are incurable primary brain tumors that affect patients of all ages. The aggressiveness of this cancer has been attributed in part to the persistence of treatment-resistant glioblastoma stem-like cells. We have previously discovered the tumor-suppressor properties of the microRNA cluster miR-302-367, representing a potential treatment for glioblastoma. Here, we attempted to develop a cell-based therapy by taking advantage of the capability of glioma cells to secrete exosomes that enclose small RNA molecules. We engineered primary glioma cells to stably express the miR-302-367. Remarkably, these cells altered, in a paracrine-dependent manner, the expression of stemness markers, the proliferation and the tumorigenicity of neighboring glioblastoma cells. Further characterization of the secretome derived from miR-302-367 expressing cells showed that a large amount of miR-302-367 was enclosed in exosomes, which were internalized by the neighboring glioblastoma cells. This miR-302-367 cell-to-cell transfer resulted in the inhibition of its targets such as CXCR4/SDF1, SHH, cyclin D, cyclin A and E2F1. Orthotopic xenograft of miR-302-367-expressing cells together with glioblastoma stem-like cells efficiently altered the tumor development in mice brain.

Dates et versions

hal-01541413 , version 1 (19-06-2017)

Identifiants

Citer

Mohamed Fareh, Fabien Almairac, Laurent Turchi, Fanny Burel-Vandenbos, Philippe Paquis, et al.. Cell-based therapy using miR-302-367 expressing cells represses glioblastoma growth. Cell Death and Disease, 2017, 8 (3), pp.e2713. ⟨10.1038/cddis.2017.117⟩. ⟨hal-01541413⟩
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