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Updated: Nov 4, 2025
An Orthotopic Bladder Cancer Model for Gene Delivery Studies
Published on: December 1, 2013
Persistent Newcastle disease virus infection in bladder cancer cells is associated with putative pro-survival and
Lee-Chin Chan1,2, Jeevanathan Kalyanasundram1, Sze-Wei Leong1
1Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, UPM, 43400, Serdang, Selangor Darul Ehsan, Malaysia.
Background:
Newcastle disease virus (NDV) is an oncolytic virus with excellent selectivity against cancer cells, both in vitro and in vivo. Unfortunately, prolonged in vitro NDV infection results in the development of persistent infection in the cancer cells which are then able to resist NDV-mediated oncolysis. However, the mechanism of persistency of infection remains poorly understood.
Methods:
In this study, we established persistently NDV-infected EJ28 bladder cancer cells, designated as EJ28P. Global transcriptomic analysis was subsequently carried out by microarray analysis. Differentially expressed genes (DEGs) between EJ28 and EJ28P cells identified by the edgeR program were further analysed by Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) analyses. In addition, the microarray data were validated by RT-qPCR.
Results:
Persistently NDV-infected EJ28 bladder cancer cells were successfully established and confirmed by flow cytometry. Microarray analysis identified a total of 368 genes as differentially expressed in EJ28P cells when compared to the non-infected EJ28 cells. GSEA revealed that the Wnt/β-catenin and KRAS signalling pathways were upregulated while the TGF-β signalling pathway was downregulated. Findings from this study suggest that the upregulation of genes that are associated with cell growth, pro-survival, and anti-apoptosis may explain the survivability of EJ28P cells and the development of persistent infection of NDV.
Conclusions:
This study provides insights into the transcriptomic changes that occur and the specific signalling pathways that are potentially involved in the development and maintenance of NDV persistency of infection in bladder cancer cells. These findings warrant further investigation and is crucial towards the development of effective NDV oncolytic therapy against cancer.
Insights
Newcastle disease virus (NDV) can infect cancer cells, but persistent infections develop, hindering oncolysis. This study identified key signaling pathways like Wnt/β-catenin and KRAS that contribute to NDV persistence in bladder cancer cells.
Area of Science:
- Oncology
- Virology
- Molecular Biology
Background:
- Newcastle disease virus (NDV) exhibits oncolytic properties against cancer cells.
- Persistent NDV infection in cancer cells leads to resistance against oncolysis.
- The mechanisms underlying NDV infection persistence are not well understood.
Purpose of the Study:
- To investigate the transcriptomic changes associated with persistent NDV infection in bladder cancer cells.
- To identify the signaling pathways involved in the development and maintenance of NDV persistence.
Main Methods:
- Established persistently NDV-infected EJ28 bladder cancer cells (EJ28P).
- Performed global transcriptomic analysis using microarray.
- Analyzed differentially expressed genes (DEGs) using Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA).
- Validated microarray data with RT-qPCR.
Main Results:
- Successfully established and confirmed persistently NDV-infected EJ28P cells.
- Identified 368 differentially expressed genes in EJ28P cells compared to EJ28 cells.
- Found upregulation of Wnt/β-catenin and KRAS signaling pathways.
- Observed downregulation of the TGF-β signaling pathway.
- Upregulation of cell growth, pro-survival, and anti-apoptosis genes suggests a mechanism for cell survivability and NDV persistence.
Conclusions:
- Provides insights into transcriptomic alterations during NDV persistence in bladder cancer.
- Identifies specific signaling pathways (Wnt/β-catenin, KRAS, TGF-β) involved in NDV persistence.
- Findings are crucial for developing effective NDV-based oncolytic therapies.
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