Journal
ONCOTARGET
Volume 8, Issue 52, Pages 90164-90175Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.21621
Keywords
microRNA; exosomes; cancer stem cells; glioma; pediatric
Categories
Funding
- Swedish Cancer Society
- Swedish Children's Cancer Society
- Swedish Research Council
- Swedish Society for Medical Research
- Wenner-Gren foundation
- Wilhelm & Martina Lundgren
- Assar Gabrielsson
- Royal Physiographic Society of Lund (The Nilsson-Ehle Endowments)
- Sahlgrenska Universitetssjukhusets fonder
- Marie Curie CIG from the EU's Seventh Framework Programme
- Cancer Research UK [17368] Funding Source: researchfish
- The Brain Tumour Charity [8/105] Funding Source: researchfish
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High-grade gliomas (HGGs) are very aggressive brain tumors with a cancer stem cell component. Cells, including cancer stem cells, release vesicles called exosomes which contain small non-coding RNAs such as microRNAs (miRNAs). These are thought to play an important role in cell-cell communication. However, we have limited knowledge of the types of exosomal miRNAs released by pediatric HGG stem cells; a prerequisite for exploring their potential roles in HGG biology. Here we isolated exosomes released by pediatric glioma stem cells (GSCs) and compared their repertoire of miRNAs to genetically normal neural stem cells (NSCs) exosomes, as well as their respective cellular miRNA content. Whereas cellular miRNAs are similar, we find that the exosomal miRNA profiles differ between normal and tumor cells, and identify several differentially expressed miRNAs. Of particular interest is miR-1290 and miR-1246, which have previously been linked to 'stemness' and invasion in other cancers. We demonstrate that GSC-secreted exosomes influence the gene expression of receiving NSCs, particularly targeting genes with a role in cell fate and tumorigenesis. Thus, our study shows that GSCs and NSCs have similar cellular miRNA profiles, yet differ significantly in the repertoire of exosomal miRNAs and these could influence malignant features of HGG.
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