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- W4382722102 endingPage "1473" @default.
- W4382722102 startingPage "1473" @default.
- W4382722102 abstract "Oncolytic viruses (OVs) are an emerging cancer therapeutic that are intended to act by selectively targeting and lysing cancerous cells and by stimulating anti-tumour immune responses, while leaving normal cells mainly unaffected. Reovirus is a well-studied OV that is undergoing advanced clinical trials and has received FDA approval in selected circumstances. However, the mechanisms governing reoviral selectivity are not well characterised despite many years of effort, including those in our accompanying paper where we characterize pathways that do not consistently modulate reoviral cytolysis. We have earlier shown that reovirus is capable of infecting and lysing both certain types of cancer cells and also cancer stem cells, and here we demonstrate its ability to also infect and kill healthy pluripotent stem cells (PSCs). This led us to hypothesize that pathways responsible for stemness may constitute a novel route for the modulation of reoviral tropism. We find that reovirus is capable of killing both murine and human embryonic and induced pluripotent stem cells. Differentiation of PSCs alters the cells’ reoviral-permissive state to a resistant one. In a breast cancer cell line that was resistant to reoviral oncolysis, induction of pluripotency programming rendered the cells permissive to cytolysis. Bioinformatic analysis indicates that expression of the Yamanaka pluripotency factors may be associated with regulating reoviral selectivity. Mechanistic insights from these studies will be useful for the advancement of reoviral oncolytic therapy." @default.
- W4382722102 created "2023-07-01" @default.
- W4382722102 creator A5017737743 @default.
- W4382722102 creator A5044638175 @default.
- W4382722102 creator A5044993479 @default.
- W4382722102 creator A5050871485 @default.
- W4382722102 creator A5063653533 @default.
- W4382722102 creator A5075718403 @default.
- W4382722102 date "2023-06-29" @default.
- W4382722102 modified "2023-09-26" @default.
- W4382722102 title "Modulation of Reoviral Cytolysis (II): Cellular Stemness" @default.
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