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Activity levels of cathepsins B and L in tumor cells are a biomarker for efficacy of reovirus-mediated tumor cell killing

Abstract

Reovirus has gained much attention as an anticancer agent; however, the mechanism of the tumor cell-specific replication of reovirus is not fully understood. Although Ras activation is known to be crucial for tumor cell-specific replication of reovirus, it remains controversial which cellular factors are required for the reovirus-mediated tumor cell killing. In this study, we systematically investigated which cellular factors determined the efficiencies of reovirus-mediated tumor cell killing in various human cultured cell lines. The efficiency of reovirus-mediated cell killing varied widely among the cell lines. Junction adhesion molecule-A, a reovirus receptor, was highly expressed in almost all cell lines examined. Ras activation levels were largely different between the cell lines; however, there were no apparent correlations among the reovirus-mediated cell killing efficiencies and Ras activation status. On the other hand, activity levels of the cysteine proteases cathepsins B and L, which are crucial for proteolytic disassembly of the outer capsid proteins of reovirus, showed a tendency to be correlated with the efficiency of reovirus-mediated cell killing. These results indicate that the activity of cathepsins B and L is the most suitable as a biomarker for the efficacy of reovirus-mediated oncolysis among the factors examined in this study.

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Acknowledgements

We would like to thank Sayuri Okamoto and Eri Hosoyamada (Osaka University, Osaka, Japan) for their help. We also would like to thank Takeshi Kobayashi (Osaka University, Osaka, Japan) for his advice. This study was supported by Grant-in-Aid for Young Scientists (A) and a Grant-in-Aid for Scientific Research (B) from Ministry of Education, Culture, Sports, Sciences and Technology of Japan.

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Correspondence to F Sakurai.

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Supplementary Information accompanies the paper on Cancer Gene Therapy website

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Terasawa, Y., Hotani, T., Katayama, Y. et al. Activity levels of cathepsins B and L in tumor cells are a biomarker for efficacy of reovirus-mediated tumor cell killing. Cancer Gene Ther 22, 188–197 (2015). https://doi.org/10.1038/cgt.2015.4

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