Multi-Omics Analysis of Glioblastoma Cells’ Sensitivity to Oncolytic Viruses

Oncolytic viruses have gained momentum in the last decades as a promising tool for cancer treatment. Despite the progress, only a fraction of patients show a positive response to viral therapy. One of the key variable factors contributing to therapy outcomes is interferon-dependent antiviral mechani...

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Autores principales:	Anastasiya V. Lipatova, Alesya V. Soboleva, Vladimir A. Gorshkov, Julia A. Bubis, Elizaveta M. Solovyeva, George S. Krasnov, Dmitry V. Kochetkov, Pavel O. Vorobyev, Irina Y. Ilina, Sergei A. Moshkovskii, Frank Kjeldsen, Mikhail V. Gorshkov, Peter M. Chumakov, Irina A. Tarasova
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	glioblastoma interferon antiviral mechanisms oncolytic viruses multi-omic approaches pathway identification Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/97c40ff905664ac59bc9aa6d36901984
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spelling	oai:doaj.org-article:97c40ff905664ac59bc9aa6d369019842021-11-11T15:26:45ZMulti-Omics Analysis of Glioblastoma Cells’ Sensitivity to Oncolytic Viruses10.3390/cancers132152682072-6694https://doaj.org/article/97c40ff905664ac59bc9aa6d369019842021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5268https://doaj.org/toc/2072-6694Oncolytic viruses have gained momentum in the last decades as a promising tool for cancer treatment. Despite the progress, only a fraction of patients show a positive response to viral therapy. One of the key variable factors contributing to therapy outcomes is interferon-dependent antiviral mechanisms in tumor cells. Here, we evaluated this factor using patient-derived glioblastoma multiforme (GBM) cultures. Cell response to the type I interferons’ (IFNs) stimulation was characterized at mRNA and protein levels. Omics analysis revealed that GBM cells overexpress interferon-stimulated genes (ISGs) and upregulate their proteins, similar to the normal cells. A conserved molecular pattern unambiguously differentiates between the preserved and defective responses. Comparing ISGs’ portraits with titration-based measurements of cell sensitivity to a panel of viruses, the “strength” of IFN-induced resistance acquired by GBM cells was ranked. The study demonstrates that suppressing a single ISG and encoding an essential antiviral protein, does not necessarily increase sensitivity to viruses. Conversely, silencing IFIT3 and PLSCR1 genes in tumor cells can negatively affect the internalization of vesicular stomatitis and Newcastle disease viruses. We present evidence of a complex relationship between the interferon response genes and other factors affecting the sensitivity of tumor cells to viruses.Anastasiya V. LipatovaAlesya V. SobolevaVladimir A. GorshkovJulia A. BubisElizaveta M. SolovyevaGeorge S. KrasnovDmitry V. KochetkovPavel O. VorobyevIrina Y. IlinaSergei A. MoshkovskiiFrank KjeldsenMikhail V. GorshkovPeter M. ChumakovIrina A. TarasovaMDPI AGarticleglioblastomainterferonantiviral mechanismsoncolytic virusesmulti-omic approachespathway identificationNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5268, p 5268 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	glioblastoma interferon antiviral mechanisms oncolytic viruses multi-omic approaches pathway identification Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	glioblastoma interferon antiviral mechanisms oncolytic viruses multi-omic approaches pathway identification Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Anastasiya V. Lipatova Alesya V. Soboleva Vladimir A. Gorshkov Julia A. Bubis Elizaveta M. Solovyeva George S. Krasnov Dmitry V. Kochetkov Pavel O. Vorobyev Irina Y. Ilina Sergei A. Moshkovskii Frank Kjeldsen Mikhail V. Gorshkov Peter M. Chumakov Irina A. Tarasova Multi-Omics Analysis of Glioblastoma Cells’ Sensitivity to Oncolytic Viruses
description	Oncolytic viruses have gained momentum in the last decades as a promising tool for cancer treatment. Despite the progress, only a fraction of patients show a positive response to viral therapy. One of the key variable factors contributing to therapy outcomes is interferon-dependent antiviral mechanisms in tumor cells. Here, we evaluated this factor using patient-derived glioblastoma multiforme (GBM) cultures. Cell response to the type I interferons’ (IFNs) stimulation was characterized at mRNA and protein levels. Omics analysis revealed that GBM cells overexpress interferon-stimulated genes (ISGs) and upregulate their proteins, similar to the normal cells. A conserved molecular pattern unambiguously differentiates between the preserved and defective responses. Comparing ISGs’ portraits with titration-based measurements of cell sensitivity to a panel of viruses, the “strength” of IFN-induced resistance acquired by GBM cells was ranked. The study demonstrates that suppressing a single ISG and encoding an essential antiviral protein, does not necessarily increase sensitivity to viruses. Conversely, silencing IFIT3 and PLSCR1 genes in tumor cells can negatively affect the internalization of vesicular stomatitis and Newcastle disease viruses. We present evidence of a complex relationship between the interferon response genes and other factors affecting the sensitivity of tumor cells to viruses.
format	article
author	Anastasiya V. Lipatova Alesya V. Soboleva Vladimir A. Gorshkov Julia A. Bubis Elizaveta M. Solovyeva George S. Krasnov Dmitry V. Kochetkov Pavel O. Vorobyev Irina Y. Ilina Sergei A. Moshkovskii Frank Kjeldsen Mikhail V. Gorshkov Peter M. Chumakov Irina A. Tarasova
author_facet	Anastasiya V. Lipatova Alesya V. Soboleva Vladimir A. Gorshkov Julia A. Bubis Elizaveta M. Solovyeva George S. Krasnov Dmitry V. Kochetkov Pavel O. Vorobyev Irina Y. Ilina Sergei A. Moshkovskii Frank Kjeldsen Mikhail V. Gorshkov Peter M. Chumakov Irina A. Tarasova
author_sort	Anastasiya V. Lipatova
title	Multi-Omics Analysis of Glioblastoma Cells’ Sensitivity to Oncolytic Viruses
title_short	Multi-Omics Analysis of Glioblastoma Cells’ Sensitivity to Oncolytic Viruses
title_full	Multi-Omics Analysis of Glioblastoma Cells’ Sensitivity to Oncolytic Viruses
title_fullStr	Multi-Omics Analysis of Glioblastoma Cells’ Sensitivity to Oncolytic Viruses
title_full_unstemmed	Multi-Omics Analysis of Glioblastoma Cells’ Sensitivity to Oncolytic Viruses
title_sort	multi-omics analysis of glioblastoma cells’ sensitivity to oncolytic viruses
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/97c40ff905664ac59bc9aa6d36901984
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Multi-Omics Analysis of Glioblastoma Cells’ Sensitivity to Oncolytic Viruses

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