학술논문
Multiomic Profiling Identified EGF Receptor Signaling as a Potential Inhibitor of Type I Interferon Response in Models of Oncolytic Therapy by Vesicular Stomatitis Virus.
Document Type
Article
Author
Nikitina, Anastasia S.; Lipatova, Anastasia V.; Goncharov, Anton O.; Kliuchnikova, Anna A.; Pyatnitskiy, Mikhail A.; Kuznetsova, Ksenia G.; Hamad, Azzam; Vorobyev, Pavel O.; Alekseeva, Olga N.; Mahmoud, Marah; Shakiba, Yasmin; Anufrieva, Ksenia S.; Arapidi, Georgy P.; Ivanov, Mark V.; Tarasova, Irina A.; Gorshkov, Mikhail V.; Chumakov, Peter M.; Moshkovskii, Sergei A.
Source
Subject
*EPIDERMAL growth factor receptors
*TYPE I interferons
*VESICULAR stomatitis
*INTERFERON receptors
*HER2 protein
*CELL receptors
*TUMOR proteins
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Language
ISSN
1661-6596
Abstract
Cancer cell lines responded differentially to type I interferon treatment in models of oncolytic therapy using vesicular stomatitis virus (VSV). Two opposite cases were considered in this study, glioblastoma DBTRG-05MG and osteosarcoma HOS cell lines exhibiting resistance and sensitivity to VSV after the treatment, respectively. Type I interferon responses were compared for these cell lines by integrative analysis of the transcriptome, proteome, and RNA editome to identify molecular factors determining differential effects observed. Adenosine-to-inosine RNA editing was equally induced in both cell lines. However, transcriptome analysis showed that the number of differentially expressed genes was much higher in DBTRG-05MG with a specific enrichment in inflammatory proteins. Further, it was found that two genes, EGFR and HER2, were overexpressed in HOS cells compared with DBTRG-05MG, supporting recent reports that EGF receptor signaling attenuates interferon responses via HER2 co-receptor activity. Accordingly, combined treatment of cells with EGF receptor inhibitors such as gefitinib and type I interferon increases the resistance of sensitive cell lines to VSV. Moreover, sensitive cell lines had increased levels of HER2 protein compared with non-sensitive DBTRG-05MG. Presumably, the level of this protein expression in tumor cells might be a predictive biomarker of their resistance to oncolytic viral therapy. [ABSTRACT FROM AUTHOR]