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

2017; American Association for Cancer Research; Volume: 77; Issue: 21 Linguagem: Inglês

10.1158/0008-5472.can-16-2524

1538-7445

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

MicroRNA in disease regulation

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.