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Cell Death Dis. 2017 Mar 30;8(3):e2713. doi: 10.1038/cddis.2017.117.

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

Author information

1
Univ. Nice Sophia Antipolis, CNRS, Inserm, iBV, Nice 06108, France.
2
Service de Neurchirurgie, Hôpital Pasteur, CHU de Nice 06107, France.
3
Service d'Anatomopathologie, Hôpital Pasteur, CHU de Nice 06107, France.
4
Centre Commun de Microscopie Electronique Appliquée, Univ. Nice Sophia Antipolis, France.
5
CNRS UMR8246 Neuroscience Paris Seine - IBPS; Team Glial Plasticity; 7 quai Saint-Bernard 75005 Paris, France.
6
Inserm U1130, Neuroscience Paris Seine - IBPS; Team Glial Plasticity; 7 quai Saint-Bernard 75005 Paris, France.
7
University Pierre and Marie Curie UMCR18, Neuroscience Paris Seine - IBPS; Team Glial Plasticity; 7 quai Saint-Bernard 75005 Paris, France.

Abstract

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.

PMID:
28358371
PMCID:
PMC5386523
DOI:
10.1038/cddis.2017.117
[Indexed for MEDLINE]
Free PMC Article

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