The oncolytic activity of Newcastle disease virus in clear cell renal carcinoma cells in normoxic and hypoxic conditions: the interplay between von Hippel-Lindau and interferon-β signaling

Viral-mediated oncolysis is a promising cancer therapeutic approach offering an increased efficacy with less toxicity than the current therapies. The complexity of solid tumor microenvironments includes regions of hypoxia. In these regions, the transcription factor, hypoxia inducible factor (HIF), i...

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Main Authors: Ch'ng, Wei Choong, Stanbridge, Eric J., Yusoff, Khatijah, Shafee, Norazizah
Format: Article
Language:English
Published: Mary Ann Liebert 2013
Online Access:http://psasir.upm.edu.my/id/eprint/28045/
http://psasir.upm.edu.my/id/eprint/28045/1/28045.pdf
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author Ch'ng, Wei Choong
Stanbridge, Eric J.
Yusoff, Khatijah
Shafee, Norazizah
author_facet Ch'ng, Wei Choong
Stanbridge, Eric J.
Yusoff, Khatijah
Shafee, Norazizah
author_sort Ch'ng, Wei Choong
building UPM Institutional Repository
collection Online Access
description Viral-mediated oncolysis is a promising cancer therapeutic approach offering an increased efficacy with less toxicity than the current therapies. The complexity of solid tumor microenvironments includes regions of hypoxia. In these regions, the transcription factor, hypoxia inducible factor (HIF), is active and regulates expression of many genes that contribute to aggressive malignancy, radio-, and chemo-resistance. To investigate the oncolytic efficacy of a highly virulent (velogenic) Newcastle disease virus (NDV) in the presence or absence of HIF-2α, renal cell carcinoma (RCC) cell lines with defective or reconstituted wild-type (wt) von Hippel-Lindau (VHL) activity were used. We show that these RCC cells responded to NDV by producing only interferon (IFN)-β, but not IFN-α, and are associated with increased STAT1 phosphorylation. Restoration of wt VHL expression enhanced NDV-induced IFN-β production, leading to prolonged STAT1 phosphorylation and increased cell death. Hypoxia augmented NDV oncolytic activity regardless of the cells' HIF-2α levels. These results highlight the potential of oncolytic NDV as a potent therapeutic agent in the killing of hypoxic cancer cells.
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spelling upm-280452016-04-21T07:28:34Z http://psasir.upm.edu.my/id/eprint/28045/ The oncolytic activity of Newcastle disease virus in clear cell renal carcinoma cells in normoxic and hypoxic conditions: the interplay between von Hippel-Lindau and interferon-β signaling Ch'ng, Wei Choong Stanbridge, Eric J. Yusoff, Khatijah Shafee, Norazizah Viral-mediated oncolysis is a promising cancer therapeutic approach offering an increased efficacy with less toxicity than the current therapies. The complexity of solid tumor microenvironments includes regions of hypoxia. In these regions, the transcription factor, hypoxia inducible factor (HIF), is active and regulates expression of many genes that contribute to aggressive malignancy, radio-, and chemo-resistance. To investigate the oncolytic efficacy of a highly virulent (velogenic) Newcastle disease virus (NDV) in the presence or absence of HIF-2α, renal cell carcinoma (RCC) cell lines with defective or reconstituted wild-type (wt) von Hippel-Lindau (VHL) activity were used. We show that these RCC cells responded to NDV by producing only interferon (IFN)-β, but not IFN-α, and are associated with increased STAT1 phosphorylation. Restoration of wt VHL expression enhanced NDV-induced IFN-β production, leading to prolonged STAT1 phosphorylation and increased cell death. Hypoxia augmented NDV oncolytic activity regardless of the cells' HIF-2α levels. These results highlight the potential of oncolytic NDV as a potent therapeutic agent in the killing of hypoxic cancer cells. Mary Ann Liebert 2013-07 Article PeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/28045/1/28045.pdf Ch'ng, Wei Choong and Stanbridge, Eric J. and Yusoff, Khatijah and Shafee, Norazizah (2013) The oncolytic activity of Newcastle disease virus in clear cell renal carcinoma cells in normoxic and hypoxic conditions: the interplay between von Hippel-Lindau and interferon-β signaling. Journal of Interferon & Cytokine Research, 33 (7). pp. 346-354. ISSN 1079-9907; ESSN: 1557-7465 http://online.liebertpub.com/doi/abs/10.1089/jir.2012.0095 10.1089/jir.2012.0095
spellingShingle Ch'ng, Wei Choong
Stanbridge, Eric J.
Yusoff, Khatijah
Shafee, Norazizah
The oncolytic activity of Newcastle disease virus in clear cell renal carcinoma cells in normoxic and hypoxic conditions: the interplay between von Hippel-Lindau and interferon-β signaling
title The oncolytic activity of Newcastle disease virus in clear cell renal carcinoma cells in normoxic and hypoxic conditions: the interplay between von Hippel-Lindau and interferon-β signaling
title_full The oncolytic activity of Newcastle disease virus in clear cell renal carcinoma cells in normoxic and hypoxic conditions: the interplay between von Hippel-Lindau and interferon-β signaling
title_fullStr The oncolytic activity of Newcastle disease virus in clear cell renal carcinoma cells in normoxic and hypoxic conditions: the interplay between von Hippel-Lindau and interferon-β signaling
title_full_unstemmed The oncolytic activity of Newcastle disease virus in clear cell renal carcinoma cells in normoxic and hypoxic conditions: the interplay between von Hippel-Lindau and interferon-β signaling
title_short The oncolytic activity of Newcastle disease virus in clear cell renal carcinoma cells in normoxic and hypoxic conditions: the interplay between von Hippel-Lindau and interferon-β signaling
title_sort oncolytic activity of newcastle disease virus in clear cell renal carcinoma cells in normoxic and hypoxic conditions: the interplay between von hippel-lindau and interferon-β signaling
url http://psasir.upm.edu.my/id/eprint/28045/
http://psasir.upm.edu.my/id/eprint/28045/
http://psasir.upm.edu.my/id/eprint/28045/
http://psasir.upm.edu.my/id/eprint/28045/1/28045.pdf