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Updated: Sep 26, 2026
An Orthotopic Bladder Cancer Model for Gene Delivery Studies
Published on: December 1, 2013
Selective reovirus killing of bladder cancer in a co-culture spheroid model
Ruhangiz T Kilani1, Yahya Tamimi, Erich G Hanel
1Division of Experimental Surgery, Department of Surgery, University of Alberta, Edmonton, AB, Canada T6G 1Z2.
Abstract:
Up to 50% of the transitional cell carcinomas (TCC) express an activated EGF pathway involving MAP/MEK and RAF kinase thus providing a novel means to selectively eliminate transformed cells expressing such proteins. This EGF pathway expression phenotype was also confirmed in our MGH-U3 and room temperature-112 human TCC cell lines, which makes them a suitable model target for the reovirus oncolysis. We report here on an in vitro assay of co-culture spheroids using either human or rat TCC cells with their corresponding fibroblasts to examine the potential of viral selective lysis for TCC. Reovirus, a respiratory enteric orphan virus, which mammals are exposed to early in life, was used in this study. Selective killing of transformed versus normal cells was assayed by time-lapse photography, vital dye staining, immunohistochemistry, and MTT assay. In this in vitro bladder cancer model, reovirus selectively destroyed the transformed cells by lysis or induction of apoptosis. Based on these findings we have initiated an in vivo pre-clinical study on intravesical administration of reovirus in an animal model to further explore the effect of reovirus-mediated oncolysis of TCC.
Insights
Reovirus selectively destroys transitional cell carcinoma (TCC) cells by targeting the activated EGF pathway. This finding supports further investigation into reovirus oncolysis for bladder cancer treatment.
Area of Science:
- Oncology
- Virology
- Molecular Biology
Background:
- Transitional cell carcinoma (TCC) often exhibits an activated Epidermal Growth Factor (EGF) pathway.
- This pathway involves MAP/MEK and RAF kinase, presenting a therapeutic target.
- Reovirus, a common virus, is being explored for its oncolytic potential.
Purpose of the Study:
- To evaluate the efficacy of reovirus in selectively targeting and eliminating TCC cells in vitro.
- To assess reovirus oncolysis in a bladder cancer model.
- To validate TCC cell lines with activated EGF pathways as suitable targets for reovirus therapy.
Main Methods:
- Utilized in vitro co-culture spheroid assays with human and rat TCC cells and fibroblasts.
- Employed time-lapse photography, vital dye staining, immunohistochemistry, and MTT assay to assess cell viability and death.
- Investigated reovirus-mediated selective lysis and apoptosis induction.
Main Results:
- Reovirus demonstrated selective destruction of transformed TCC cells in the in vitro bladder cancer model.
- Viral lysis and induction of apoptosis were observed in TCC cells.
- Normal fibroblasts were spared, indicating selective targeting.
Conclusions:
- Reovirus effectively and selectively eliminates TCC cells in vitro by exploiting the activated EGF pathway.
- These findings support the potential of reovirus oncolysis as a novel therapeutic strategy for bladder cancer.
- An in vivo preclinical study has been initiated to further explore intravesical reovirus administration for TCC.
