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N-Myc expression enhances the oncolytic effects of vesicular stomatitis virus in human neuroblastoma cells

N-myc oncogene amplification is associated but not present in all cases of high-risk neuroblastoma (NB). Since oncogene expression could often modulate sensitivity to oncolytic viruses, we wanted to examine if N-myc expression status would determine virotherapy efficacy to high-risk NB. We showed th...

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Autores principales: Corredor, Juan C, Redding, Nicole, Bloté, Karen, Robbins, Stephen M, Senger, Donna L, Bell, John C, Beaudry, Paul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5008254/
https://www.ncbi.nlm.nih.gov/pubmed/27626059
http://dx.doi.org/10.1038/mto.2016.5
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author Corredor, Juan C
Redding, Nicole
Bloté, Karen
Robbins, Stephen M
Senger, Donna L
Bell, John C
Beaudry, Paul
author_facet Corredor, Juan C
Redding, Nicole
Bloté, Karen
Robbins, Stephen M
Senger, Donna L
Bell, John C
Beaudry, Paul
author_sort Corredor, Juan C
collection PubMed
description N-myc oncogene amplification is associated but not present in all cases of high-risk neuroblastoma (NB). Since oncogene expression could often modulate sensitivity to oncolytic viruses, we wanted to examine if N-myc expression status would determine virotherapy efficacy to high-risk NB. We showed that induction of exogenous N-myc in a non-N-myc-amplified cell line background (TET-21N) increased susceptibility to oncolytic vesicular stomatitis virus (mutant VSVΔM51) and alleviated the type I IFN-induced antiviral state. Cells with basal N-myc, on the other hand, were less susceptible to virus-induced oncolysis and established a robust IFN-mediated antiviral state. The same effects were also observed in NB cell lines with and without N-myc amplification. Microarray analysis showed that N-myc overexpression in TET-21N cells downregulated IFN-stimulated genes (ISGs) with known antiviral functions. Furthermore, virus infection caused significant changes in global gene expression in TET-21N cells overexpressing N-myc. Such changes involved ISGs with various functions. Therefore, the present study showed that augmented susceptibility to VSVΔM51 by N-myc at least involves downregulation of ISGs with antiviral functions and alleviation of the IFN-stimulated antiviral state. Our studies suggest the potential utility of N-myc amplification/overexpression as a predictive biomarker of virotherapy response for high-risk NB using IFN-sensitive oncolytic viruses.
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spelling pubmed-50082542016-09-13 N-Myc expression enhances the oncolytic effects of vesicular stomatitis virus in human neuroblastoma cells Corredor, Juan C Redding, Nicole Bloté, Karen Robbins, Stephen M Senger, Donna L Bell, John C Beaudry, Paul Mol Ther Oncolytics Article N-myc oncogene amplification is associated but not present in all cases of high-risk neuroblastoma (NB). Since oncogene expression could often modulate sensitivity to oncolytic viruses, we wanted to examine if N-myc expression status would determine virotherapy efficacy to high-risk NB. We showed that induction of exogenous N-myc in a non-N-myc-amplified cell line background (TET-21N) increased susceptibility to oncolytic vesicular stomatitis virus (mutant VSVΔM51) and alleviated the type I IFN-induced antiviral state. Cells with basal N-myc, on the other hand, were less susceptible to virus-induced oncolysis and established a robust IFN-mediated antiviral state. The same effects were also observed in NB cell lines with and without N-myc amplification. Microarray analysis showed that N-myc overexpression in TET-21N cells downregulated IFN-stimulated genes (ISGs) with known antiviral functions. Furthermore, virus infection caused significant changes in global gene expression in TET-21N cells overexpressing N-myc. Such changes involved ISGs with various functions. Therefore, the present study showed that augmented susceptibility to VSVΔM51 by N-myc at least involves downregulation of ISGs with antiviral functions and alleviation of the IFN-stimulated antiviral state. Our studies suggest the potential utility of N-myc amplification/overexpression as a predictive biomarker of virotherapy response for high-risk NB using IFN-sensitive oncolytic viruses. Nature Publishing Group 2016-03-16 /pmc/articles/PMC5008254/ /pubmed/27626059 http://dx.doi.org/10.1038/mto.2016.5 Text en Copyright © 2016 Official journal of the American Society of Gene & Cell Therapy http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/
spellingShingle Article
Corredor, Juan C
Redding, Nicole
Bloté, Karen
Robbins, Stephen M
Senger, Donna L
Bell, John C
Beaudry, Paul
N-Myc expression enhances the oncolytic effects of vesicular stomatitis virus in human neuroblastoma cells
title N-Myc expression enhances the oncolytic effects of vesicular stomatitis virus in human neuroblastoma cells
title_full N-Myc expression enhances the oncolytic effects of vesicular stomatitis virus in human neuroblastoma cells
title_fullStr N-Myc expression enhances the oncolytic effects of vesicular stomatitis virus in human neuroblastoma cells
title_full_unstemmed N-Myc expression enhances the oncolytic effects of vesicular stomatitis virus in human neuroblastoma cells
title_short N-Myc expression enhances the oncolytic effects of vesicular stomatitis virus in human neuroblastoma cells
title_sort n-myc expression enhances the oncolytic effects of vesicular stomatitis virus in human neuroblastoma cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5008254/
https://www.ncbi.nlm.nih.gov/pubmed/27626059
http://dx.doi.org/10.1038/mto.2016.5
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