Journal
ONCOTARGET
Volume 9, Issue 2, Pages 1785-1802Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.22751
Keywords
comparative proteomics; glioblastoma multiforme; oncolytic virotherapy; interferon signaling alterations; JAK/STAT pathway
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Funding
- Russian Science Foundation [14-50-00060, 14-14-00971]
- European Research Council (ERC) under the European Union [646603]
- Danish Council for Independent Research [0602-02691B]
- VILLUM Center for Bioanalytical Sciences at the University of Southern Denmark
- Federal Agency of Scientific Organizations, Russia [1]
- Villum Fonden [00007292] Funding Source: researchfish
- Russian Science Foundation [17-14-00076] Funding Source: Russian Science Foundation
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An acquisition of increased sensitivity of cancer cells to viruses is a common outcome of malignant progression that justifies the development of oncolytic viruses as anticancer therapeutics. Studying molecular changes that underlie the sensitivity to viruses would help to identify cases where oncolytic virus therapy would be most effective. We quantified changes in protein abundances in two glioblastoma multiforme (GBM) cell lines that differ in the ability to induce resistance to vesicular stomatitis virus (VSV) infection in response to type I interferon (IFN) treatment. In IFN-treated samples we observed an up-regulation of protein products of some IFN-regulated genes (IRGs). In total, the proteome analysis revealed up to 20% more proteins encoded by IRGs in the glioblastoma cell line, which develops resistance to VSV infection after pre-treatment with IFN. In both cell lines protein-protein interaction and signaling pathway analyses have revealed a significant stimulation of processes related to type I IFN signaling and defense responses to viruses. However, we observed a deficiency in STAT2 protein in the VSV-sensitive cell line that suggests a de-regulation of the JAK/STAT/IRF9 signaling. The study has shown that the up-regulation of IRG proteins induced by the IFN alpha treatment of GBM cells can be detected at the proteome level. Similar analyses could be applied for revealing functional alterations within the antiviral mechanisms in glioblastoma samples, accompanying by acquisition of sensitivity to oncolytic viruses. The approach can be useful for discovering the biomarkers that predict a potential sensitivity of individual glioblastoma tumors to oncolytic virus therapy.
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