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.