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

被引：46

作者：

Tuzesi, Agota ^{[1
]}

Kling, Teresia ^{[1
]}

Wenger, Anna ^{[1
]}

Lunavat, Taral R. ^{[2
]}

Jang, Su Chul ^{[2
]}

Rydenhag, Bertil ^{[3
]}

Lotvall, Jan ^{[2
]}

Pollard, Steven M. ^{[4
]}

Danielsson, Anna ^{[5
]}

Caren, Helena ^{[1
]}

机构：

[1] Univ Gothenburg, Sahlgrenska Acad, Inst Biomed, Sahlgrenska Canc Ctr,Dept Pathol & Genet, Gothenburg, Sweden

[2] Univ Gothenburg, Dept Internal Med & Clin Nutr, Krefting Res Ctr, Gothenburg, Sweden

[3] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Clin Neurosci, Gothenburg, Sweden

[4] Univ Edinburgh, MRC Ctr Regenerat Med, Edinburgh BioQuarter, Edinburgh, Midlothian, Scotland

[5] Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Sahlgrenska Canc Ctr,Dept Oncol, Gothenburg, Sweden

来源：

ONCOTARGET | 2017年 / 8卷 / 52期

基金：

瑞典研究理事会;

关键词：

microRNA; exosomes; cancer stem cells; glioma; pediatric; EXTRACELLULAR VESICLES; INVASION; PROLIFERATION; EXPRESSION; MICRORNAS; DIFFERENTIATION; MIGRATION; STEMNESS; TOOLS; RNA;

D O I：

10.18632/oncotarget.21621

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：90164 / 90175

页数：12

共 45 条

[1] Survey of MicroRNA Expression in Pediatric Brain Tumors [J].

Birks, Diane K. ;

Barton, Valerie N. ;

Donson, Andrew M. ;

Handler, Michael H. ;

Vibhakar, Rajeev ;

Foreman, Nicholas K. .

PEDIATRIC BLOOD & CANCER, 2011, 56 (02) :211-216

[2] msa: an R package for multiple sequence alignment [J].

Bodenhofer, Ulrich ;

Bonatesta, Enrico ;

Horejs-Kainrath, Christoph ;

Hochreiter, Sepp .

BIOINFORMATICS, 2015, 31 (24) :3997-3999

[3] miR-15a and miR-24-1 as putative prognostic microRNA signatures for pediatric pilocytic astrocytomas and ependymomas [J].

Braoudaki, M. ;

Lambrou, G. I. ;

Giannikou, K. ;

Papadodima, S. A. ;

Lykoudi, A. ;

Stefanaki, K. ;

Sfakianos, G. ;

Kolialexi, A. ;

Tzortzatou-Stathopoulou, F. ;

Tzetis, M. ;

Kitsiou-Tzeli, S. ;

Kanavakis, E. .

TUMOR BIOLOGY, 2016, 37 (07) :9887-9897

[4] Glioblastoma Stem Cells Respond to Differentiation Cues but Fail to Undergo Commitment and Terminal Cell-Cycle Arrest [J].

Caren, Helena ;

Stricker, Stefan H. ;

Bulstrode, Harry ;

Gagrica, Sladjana ;

Johnstone, Ewan ;

Bartlett, Thomas E. ;

Feber, Andrew ;

Wilson, Gareth ;

Teschendorff, Andrew E. ;

Bertone, Paul ;

Beck, Stephan ;

Pollard, Steven M. .

STEM CELL REPORTS, 2015, 5 (05) :829-842

[5] MiR-1246 promotes SiHa cervical cancer cell proliferation, invasion, and migration through suppression of its target gene thrombospondin 2 [J].

Chen, Junying ;

Yao, Desheng ;

Zhao, Shan ;

He, Chanjuan ;

Ding, Nan ;

Li, Li ;

Long, Fengyi .

ARCHIVES OF GYNECOLOGY AND OBSTETRICS, 2014, 290 (04) :725-732

[6] Comprehensive genomic characterization defines human glioblastoma genes and core pathways [J].

Chin, L. ;

Meyerson, M. ;

Aldape, K. ;

Bigner, D. ;

Mikkelsen, T. ;

VandenBerg, S. ;

Kahn, A. ;

Penny, R. ;

Ferguson, M. L. ;

Gerhard, D. S. ;

Getz, G. ;

Brennan, C. ;

Taylor, B. S. ;

Winckler, W. ;

Park, P. ;

Ladanyi, M. ;

Hoadley, K. A. ;

Verhaak, R. G. W. ;

Hayes, D. N. ;

Spellman, Paul T. ;

Absher, D. ;

Weir, B. A. ;

Ding, L. ;

Wheeler, D. ;

Lawrence, M. S. ;

Cibulskis, K. ;

Mardis, E. ;

Zhang, Jinghui ;

Wilson, R. K. ;

Donehower, L. ;

Wheeler, D. A. ;

Purdom, E. ;

Wallis, J. ;

Laird, P. W. ;

Herman, J. G. ;

Schuebel, K. E. ;

Weisenberger, D. J. ;

Baylin, S. B. ;

Schultz, N. ;

Yao, Jun ;

Wiedemeyer, R. ;

Weinstein, J. ;

Sander, C. ;

Gibbs, R. A. ;

Gray, J. ;

Kucherlapati, R. ;

Lander, E. S. ;

Myers, R. M. ;

Perou, C. M. ;

McLendon, Roger .

NATURE, 2008, 455 (7216) :1061-1068

[7] Downregulation of TLX induces TET3 expression and inhibits glioblastoma stem cell self-renewal and tumorigenesis [J].

Cui, Qi ;

Yang, Su ;

Ye, Peng ;

Tian, E. ;

Sun, Guoqiang ;

Zhou, Jiehua ;

Sun, Guihua ;

Liu, Xiaoxuan ;

Chen, Chao ;

Murai, Kiyohito ;

Zhao, Chunnian ;

Azizian, Krist T. ;

Yang, Lu ;

Warden, Charles ;

Wu, Xiwei ;

D'Apuzzo, Massimo ;

Brown, Christine ;

Badie, Behnam ;

Peng, Ling ;

Riggs, Arthur D. ;

Rossi, John J. ;

Shi, Yanhong .

NATURE COMMUNICATIONS, 2016, 7

[8] PTEN signaling in brain: neuropathology and tumorigenesis [J].

Endersby, R. ;

Baker, S. J. .

ONCOGENE, 2008, 27 (41) :5416-5430

[9] Oncomirs - microRNAs with a role in cancer [J].

Esquela-Kerscher, A ;

Slack, FJ .

NATURE REVIEWS CANCER, 2006, 6 (04) :259-269

[10] Pediatric high grade glioma: a review and update on tumor clinical characteristics and biology [J].

Fangusaro, Jason .

FRONTIERS IN ONCOLOGY, 2012, 2

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