Exosomes from glioma-associated mesenchymal stem cells increase the tumorigenicity of glioma stem-like cells via transfer of miR-1587

  • Javier Figueroa
  • , Lynette M. Phillips
  • , Tal Shahar
  • , Anwar Hossain
  • , Joy Gumin
  • , Hoon Kim
  • , Andrew J. Bean
  • , George A. Calin
  • , Juan Fueyo
  • , Edgar T. Walters
  • , Raghu Kalluri
  • , Roel G. Verhaak
  • , Frederick F. Lang

Research output: Contribution to journalArticlepeer-review

203 Scopus citations

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.

Original languageEnglish
Pages (from-to)5808-5819
Number of pages12
JournalCancer Research
Volume77
Issue number21
DOIs
StatePublished - 1 Nov 2017
Externally publishedYes

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