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

Artikel i vetenskaplig tidskrift
Författare Ágota Tüzesi
Teresia Kling
Anna Wenger
Taral R Lunavat
Su Chul Jang
Bertil Rydenhag
Jan Lötvall
S. M. Pollard
Anna Danielsson
Helena Carén
Publicerad i Oncotarget
Volym 8
Nummer/häfte 52
Sidor 90164-90175
ISSN 1949-2553
Publiceringsår 2017
Publicerad vid Institutionen för kliniska vetenskaper, Avdelningen för onkologi
Institutionen för biomedicin, avdelningen för patologi
Sahlgrenska Cancer Center
Krefting Research Centre
Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap
Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition
Sidor 90164-90175
Språk en
Länkar dx.doi.org/10.18632/oncotarget.2162...
Ämnesord 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
Ämneskategorier Cancer och onkologi

Sammanfattning

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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