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Pediatric brain tumor cells release exosomes with a miRNA repertoire that differs from exosomes secreted by normal cells

Journal article
Authors Ágota Tüzesi
Teresia Kling
Anna Wenger
Taral R Lunavat
Su Chul Jang
Bertil Rydenhag
Jan Lötvall
S. M. Pollard
Anna Danielsson
Helena Carén
Published in Oncotarget
Volume 8
Issue 52
Pages 90164-90175
ISSN 1949-2553
Publication year 2017
Published at Institute of Clinical Sciences, Department of Oncology
Institute of Biomedicine, Department of Pathology
Sahlgrenska Cancer Center
Krefting Research Centre
Institute of Neuroscience and Physiology, Department of Clinical Neuroscience
Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
Pages 90164-90175
Language en
Links dx.doi.org/10.18632/oncotarget.2162...
Keywords Cancer stem cells, Exosomes, Glioma, microRNA, Pediatric, microRNA 1246, microRNA 1290, unclassified drug, Article, brain tumor cell line, cancer stem cell, carcinogenesis, cell fate, cell invasion, cell isolation, cellular secretion, child, childhood cancer, controlled study, exosome, gene expression, gene function, gene targeting, glioma stem cell, human, human cell, neural stem cell, RNA analysis
Subject categories Cancer and Oncology

Abstract

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. © Tuzesi et al.

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