Glioblastoma extracellular vesicles induce the tumour-promoting transformation of neural stem cells

Wang, Jian; Liu, Jialin; Sun, Guochen; Meng, Hao; Wang, Jiayin; Guan, Yunqian; Yin, Yuzhen; Zhao, Zhenyu; Dong, Xian‐Zhe; Yin, Shangjiong; Li, Hongwei; Cheng, Yuefei; Wu, Hao; Wu, Anhua; Yu, Xinguang; Chen, Ling

doi:10.1016/j.canlet.2019.09.004

Cited by 35 publications

(29 citation statements)

References 50 publications

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“…Regulation of EV release is critical for cellular communication and modulation of the microenvironment in cancer progression and metastasis and recognised to be of increasing importance in GBM [21,22]. GBM-derived EVs have furthermore been shown to induce tumour-promoting transformation of subventricular zone resident neural stem cells, possibly contributing to GBM recurrence [64]. Differences in EV release profiles between GBM cell lines, including EV sub-populations and during normal growth conditions, have previously been reported by us and others [9,38,65].…”

Section: Discussionmentioning

confidence: 99%

Peptidylarginine Deiminase Isozyme-Specific PAD2, PAD3 and PAD4 Inhibitors Differentially Modulate Extracellular Vesicle Signatures and Cell Invasion in Two Glioblastoma Multiforme Cell Lines

Uysal-Onganer

MacLatchy

Rayan

et al. 2020

IJMS

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Glioblastoma multiforme (GBM) is an aggressive adult brain tumour with poor prognosis. Roles for peptidylarginine deiminases (PADs) in GBM have recently been highlighted. Here, two GBM cell lines were treated with PAD2, PAD3 and PAD4 isozyme-specific inhibitors. Effects were assessed on extracellular vesicle (EV) signatures, including EV-microRNA cargo (miR21, miR126 and miR210), and on changes in cellular protein expression relevant for mitochondrial housekeeping (prohibitin (PHB)) and cancer progression (stromal interaction molecule 1 (STIM-1) and moesin), as well as assessing cell invasion. Overall, GBM cell-line specific differences for the three PAD isozyme-specific inhibitors were observed on modulation of EV-signatures, PHB, STIM-1 and moesin protein levels, as well as on cell invasion. The PAD3 inhibitor was most effective in modulating EVs to anti-oncogenic signatures (reduced miR21 and miR210, and elevated miR126), to reduce cell invasion and to modulate protein expression of pro-GBM proteins in LN229 cells, while the PAD2 and PAD4 inhibitors were more effective in LN18 cells. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for deiminated proteins relating to cancer, metabolism and inflammation differed between the two GBM cell lines. Our findings highlight roles for the different PAD isozymes in the heterogeneity of GBM tumours and the potential for tailored PAD-isozyme specific treatment.

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Section: Discussionmentioning

confidence: 99%

Peptidylarginine Deiminase Isozyme-Specific PAD2, PAD3 and PAD4 Inhibitors Differentially Modulate Extracellular Vesicle Signatures and Cell Invasion in Two Glioblastoma Multiforme Cell Lines

Uysal-Onganer

MacLatchy

Rayan

et al. 2020

IJMS

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“…Then, the cDNA library was successfully constructed and sequenced [33][34][35]. Although high-throughput sequencing technology has been widely used, there are still some sequencing errors that are affected by many factors, such as the sequencer itself, sequencing reagents, and samples [36][37][38]. At present, the researchers found that in RNA-seq, the longer the sequence, the higher the probability of recognition errors.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome analysis of differential gene expression in the longissimus dorsi muscle from Debao and landrace pigs based on RNA-sequencing

Song

Zeng

et al. 2019

Bioscience Reports

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RNA-seq analysis was used to identify differentially expressed genes (DEGs) at the genetic level in the longissimus dorsi muscle from two pigs to investigate the genetic mechanisms underlying the difference in meat quality between Debao pigs and Landrace pigs. Then, these DEGs underwent functional annotation, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and protein–protein interaction (PPI) analyses. Finally, the expression levels of specific DEGs were assessed using qRT-PCR. The reference genome showed gene dosage detection of all samples which showed that the total reference genome comprised 22342 coding genes, including 14743 known and 190 unknown genes. For detection of the Debao pig genome, we obtained 14168 genes, including 13994 known and 174 unknown genes. For detection of the Landrace pig genome, we obtained 14404 genes, including 14223 known and 181 unknown genes. GO analysis and KEGG signaling pathway analysis show that DEGs are significantly related to metabolic regulation, amino acid metabolism, muscular tissue, muscle structure development etc. We identified key genes in these processes, such as FOS, EGR2, and IL6, by PPI network analysis. qRT-PCR confirmed the differential expression of six selected DEGs in both pig breeds. In conclusion, the present study revealed key genes and related signaling pathways that influence the difference in pork quality between these breeds and could provide a theoretical basis for improving pork quality in future genetic thremmatology.

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“…It is therefore feasible that astrocyte-like stem cells of the subventricular zone may acquire GSC features as a result of receiving instructive signals from EVs of variable origin. It is worth mentioning the recent study by Wang and colleagues [70] in which they demonstrate that GBM-derived EVs induce the transformation of human embryonic neural stem cells into tumor-promoting cells.…”

Section: Effects On Astrocytesmentioning

confidence: 99%

Extracellular Vesicle-Mediated Communication between the Glioblastoma and Its Microenvironment

Matarredona

Pastor

2019

Cells

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The glioblastoma is the most malignant form of brain cancer. Glioblastoma cells use multiple ways of communication with the tumor microenvironment in order to tune it for their own benefit. Among these, extracellular vesicles have emerged as a focus of study in the last few years. Extracellular vesicles contain soluble proteins, DNA, mRNA and non-coding RNAs with which they can modulate the phenotypes of recipient cells. In this review we summarize recent findings on the extracellular vesicles-mediated bilateral communication established between glioblastoma cells and their tumor microenvironment, and the impact of this dialogue for tumor progression and recurrence.

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Glioblastoma extracellular vesicles induce the tumour-promoting transformation of neural stem cells

Cited by 35 publications

References 50 publications

Peptidylarginine Deiminase Isozyme-Specific PAD2, PAD3 and PAD4 Inhibitors Differentially Modulate Extracellular Vesicle Signatures and Cell Invasion in Two Glioblastoma Multiforme Cell Lines

Peptidylarginine Deiminase Isozyme-Specific PAD2, PAD3 and PAD4 Inhibitors Differentially Modulate Extracellular Vesicle Signatures and Cell Invasion in Two Glioblastoma Multiforme Cell Lines

Transcriptome analysis of differential gene expression in the longissimus dorsi muscle from Debao and landrace pigs based on RNA-sequencing

Extracellular Vesicle-Mediated Communication between the Glioblastoma and Its Microenvironment

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