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

International Journal of Molecular Sciences

Azzam Hamad¹  Olga N. Alekseeva¹  Peter M. Chumakov¹  Pavel O. Vorobyev¹  Anastasia V. Lipatova¹  Ksenia S. Anufrieva²  Mikhail A. Pyatnitskiy²  Anna A. Kliuchnikova²  Anton O. Goncharov²  Ksenia G. Kuznetsova²  Anastasia S. Nikitina²  Georgy P. Arapidi²  Sergei A. Moshkovskii²  Marah Mahmoud³  Yasmin Shakiba³  Mark V. Ivanov⁴  Mikhail V. Gorshkov⁴  Irina A. Tarasova⁴ 

[1] Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia;Federal Research and Clinical Center of Physical-Chemical Medicine, 119435 Moscow, Russia;Moscow Institute of Physics and Technology, 141700 Dolgoprudniy, Russia;V.L. Talrose Institute for Energy Problems of Chemical Physics, N.N. Semenov Federal Research Center for Chemical Physics, Russian Academy of Sciences, 119334 Moscow, Russia;

关键词: oncolytic virus;    vesicular stomatitis virus;    glioblastoma;    osteosarcoma;    type I interferon;    epidermal growth factor receptor;   

DOI  :  10.3390/ijms23095244

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown