title: Cell-based therapy using miR-302-367 expressing cells represses glioblastoma growth.
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.
authors.affiliation: Univ. Nice Sophia Antipolis, CNRS, Inserm, iBV, Nice 06108, France.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Fareh
authors.affiliation: Univ. Nice Sophia Antipolis, CNRS, Inserm, iBV, Nice 06108, France.|Service de Neurchirurgie, Hôpital Pasteur, CHU de Nice 06107, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Almairac
authors.affiliation: Univ. Nice Sophia Antipolis, CNRS, Inserm, iBV, Nice 06108, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Turchi
authors.affiliation: Univ. Nice Sophia Antipolis, CNRS, Inserm, iBV, Nice 06108, France.|Service d'Anatomopathologie, Hôpital Pasteur, CHU de Nice 06107, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Burel-Vandenbos
authors.affiliation: Univ. Nice Sophia Antipolis, CNRS, Inserm, iBV, Nice 06108, France.|Service de Neurchirurgie, Hôpital Pasteur, CHU de Nice 06107, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Paquis
authors.affiliation: Service de Neurchirurgie, Hôpital Pasteur, CHU de Nice 06107, France.
authors.forename: Denys
authors.initials: D
authors.lastname: Fontaine
authors.affiliation: Centre Commun de Microscopie Electronique Appliquée, Univ. Nice Sophia Antipolis, France.
authors.forename: Sandra
authors.initials: S
authors.lastname: Lacas-Gervais
authors.affiliation: CNRS UMR8246 Neuroscience Paris Seine - IBPS; Team Glial Plasticity; 7 quai Saint-Bernard 75005 Paris, France.|Inserm U1130, Neuroscience Paris Seine - IBPS; Team Glial Plasticity; 7 quai Saint-Bernard 75005 Paris, France.|University Pierre and Marie Curie UMCR18, Neuroscience Paris Seine - IBPS; Team Glial Plasticity; 7 quai Saint-Bernard 75005 Paris, France.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Junier
authors.affiliation: CNRS UMR8246 Neuroscience Paris Seine - IBPS; Team Glial Plasticity; 7 quai Saint-Bernard 75005 Paris, France.|Inserm U1130, Neuroscience Paris Seine - IBPS; Team Glial Plasticity; 7 quai Saint-Bernard 75005 Paris, France.|University Pierre and Marie Curie UMCR18, Neuroscience Paris Seine - IBPS; Team Glial Plasticity; 7 quai Saint-Bernard 75005 Paris, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Chneiweiss
authors.affiliation: Univ. Nice Sophia Antipolis, CNRS, Inserm, iBV, Nice 06108, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Virolle
mesh_terms: D000818:Animals; D064987:Cell- and Tissue-Based Therapy; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D005810:Multigene Family; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm