Exosomes from Glioma-Associated Mesenchymal Stem Cells Increase the Tumorigenicity of Glioma Stem-like Cells via Transfer of miR-1587.

Tumor–stromal communications impact tumorigenesis in ways that are incompletely understood. Here, we show that glioma-associated human mesenchymal stem cells (GA-hMSC), a newly identified stromal component of glioblastoma, release exosomesthat increase the proliferation and clonogenicity of tumor-initiatingglioma stem-like cells (GSC). This event leads to a significantly greater tumor burden and decreased host survival compared with untreated GSCs in orthotopic xenografts. Analysis of the exosomalcontent identified miR-1587 as a mediator of the exosomaleffects on GSCs, in part via downregulation of the tumor-suppressive nuclear receptor corepressorNCOR1. Our results illuminate the tumor-supporting role for GA-hMSCs by identifying GA-hMSC–derived exosomesin the intercellular transfer of specific miRNA that enhance the aggressiveness of glioblastoma. Cancer Res; 77(21); 5808–19. ©2017 AACR .