Multiomic Profiling Identified EGF Receptor Signaling as a Potential Inhibitor of Type I Interferon Response in Models of Oncolytic Therapy by Vesicular Stomatitis Virus

Multiomic Profiling Identified EGF Receptor Signaling as a Potential Inhibitor of Type I Interferon Response in Models of Oncolytic Therapy by Vesicular Stomatitis Virus

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 afte...

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Main Authors: Anastasia S. Nikitina, Anastasia V. Lipatova, Anton O. Goncharov, Anna A. Kliuchnikova, Mikhail A. Pyatnitskiy, Ksenia G. Kuznetsova, Azzam Hamad, Pavel O. Vorobyev, Olga N. Alekseeva, Marah Mahmoud, Yasmin Shakiba, Ksenia S. Anufrieva, Georgy P. Arapidi, Mark V. Ivanov, Irina A. Tarasova, Mikhail V. Gorshkov, Peter M. Chumakov, Sergei A. Moshkovskii
Format: Article
Language:English
Published: MDPI AG 2022-05-01
Series:International Journal of Molecular Sciences
Subjects:
oncolytic virus
vesicular stomatitis virus
glioblastoma
osteosarcoma
type I interferon
epidermal growth factor receptor
Online Access:https://www.mdpi.com/1422-0067/23/9/5244
Description
Summary: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.
ISSN:1661-6596
1422-0067

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