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

Cancer Res. 2017 Nov 1;77(21):5808-5819. doi: 10.1158/0008-5472.CAN-16-2524. Epub 2017 Aug 30.

Abstract

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 exosomes that increase the proliferation and clonogenicity of tumor-initiating glioma 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 exosomal content identified miR-1587 as a mediator of the exosomal effects on GSCs, in part via downregulation of the tumor-suppressive nuclear receptor corepressor NCOR1. Our results illuminate the tumor-supporting role for GA-hMSCs by identifying GA-hMSC-derived exosomes in the intercellular transfer of specific miRNA that enhance the aggressiveness of glioblastoma. Cancer Res; 77(21); 5808-19. ©2017 AACR.

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Transformation, Neoplastic*
  • Cells, Cultured
  • Exosomes / genetics*
  • Exosomes / metabolism
  • Exosomes / ultrastructure
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic
  • Glioma / genetics*
  • Glioma / metabolism
  • Glioma / pathology
  • Humans
  • Mesenchymal Stem Cells / metabolism*
  • Mice, Nude
  • MicroRNAs / genetics*
  • Microscopy, Electron
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / transplantation
  • Nuclear Receptor Co-Repressor 1 / genetics
  • Nuclear Receptor Co-Repressor 1 / metabolism
  • Stem Cell Transplantation / methods
  • Transplantation, Heterologous

Substances

  • MIRN1587 microRNA, human
  • MicroRNAs
  • NCOR1 protein, human
  • Nuclear Receptor Co-Repressor 1