Tumor-stromal communications impact tumorigenesis in ways that are incompletely understood. In a recent report, researchers from the University of Texas MD Anderson Cancer Center showed 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 using miRNA microarray 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
GA-hMSC–derived exosomes contain a unique miRNA profile
A and B, miRNA profiles for GA-hMSC and GA-hMSC–derived exosomes, demonstrating a significant (P < 0.001) difference in miRNA content. A, Three hundred and twenty miRNAs were selected by identifying the top 200 miRNAs for each pair of GA-hMSC and GA-hMSC–derived exosomes according to the absolute fold change and collapsing them into nonduplicated miRNAs. B, The top 20 miRNAs and the 8 miRNAs that were highly expressed and highly enriched in exosomes were selected as in A and subjected to cluster analysis. C, Distribution of the average expression level for miRNA in exosomes four GA-HMSC lines, compared with the parental cell. Exosome-enriched miRNAs were both highly expressed (>5,000 hybridization intensity) and highly enriched (>3.0 SD) compared with exosome-depleted miRNA, which were both highly expressed (>5,000 hybridization intensity) and highly enriched (<−1.0 SD) in parental cells. D, Expression levels of predicted gene targets of the exosomal miRNA are significantly (P < 0.01) decreased in GSCs after treatment with GA-hMSC–derived exosomes. Exo, exosome.
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Reference
J. Figueroa, L. M. Phillips, T. Shahar, R. G. Verhaak F. K. Lang, et al. (2017) Exosomes from Glioma-Associated Mesenchymal Stem Cells Increase the Tumorigenicity of Glioma Stem-like Cells via Transfer of miR-1587 American Association for Cancer Research doi: 10.1158/0008-5472.CAN-16-2524 [abstract]