Exosomes transfer specific miRNA that enhance the aggressiveness of glioblastoma

Tumor-stromal communications impact tumorigenesis in ways that are incompletely understood. Here researchers from the MD Anderson Cancer Center show that Glioma Associated-human Mesenchymal Stem Cells (GA-hMSCs), a newly identified stromal component of glioblastoma, release exosomes that increase the proliferation and clonogenicity of tumor-initiating Glioma Stem-like Cells (GSCs). 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 down-regulation of the tumor suppressive nuclear receptor co-repressor NCOR1. These 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.

Summary Schemata

exosomes

BM-hMSCs are attracted to gliomas and become GAhMSCs within the tumor niche. These GA-hMSCs preferentially package miR-1587 into exosomes, which are released by the GA-hMSCs and taken up by neighboring GSCs. The increased level of miR-1587 down-regulates NCOR1 levels in GSCs. These effects ultimately result in increased GSC proliferation and clonogenicity, and subsequently increases tumor growth.

Figueroa J, Phillips LM, Shahar T, Hossain A, Gumin J, Kim H, Bean AJ, Calin GA, Fueyo J, Walters ET, Kalluri R, Verhaak RG, Lang FF. (2017) Exosomes from Glioma-Associated Mesenchymal Stem Cells Increase the Tumorigenicity of Glioma Stem-like Cells via Transfer of miR-1587. Cancer Res 77(21):5808-5819. [abstract]

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