title: 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.
authors: Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
authors: Y
authors: Y
authors: Terasawa
authors: Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
authors: T
authors: T
authors: Hotani
authors: Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
authors: Y
authors: Y
authors: Katayama
authors: Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
authors: M
authors: M
authors: Tachibana
authors: 1] Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan [2] Laboratory of Hepatic Differentiation Research, National Institute of Biomedical Innovation, Osaka, Japan [3] Center for Advanced Medical Engineering and Informatics, Osaka University, Osaka, Japan [4] Laboratory of iPS Research, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
authors: H
authors: H
authors: Mizuguchi
authors: 1] Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan [2] Laboratory of Regulatory Sciences for Oligonucleotide Therapeutics, Clinical Drug Development Unit, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
authors: F
authors: F
authors: Sakurai
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D036022:Capsid Proteins / Q000378:metabolism; D002401:Cathepsin B / Q000378:metabolism*; D056668:Cathepsin L / Q000378:metabolism*; D002470:Cell Survival; D004789:Enzyme Activation; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D007113:Immunity, Innate; D061986:MCF-7 Cells; D051379:Mice; D030102:Orthoreovirus, Mammalian / Q000276:immunology / Q000502:physiology*; D059748:Proteolysis; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D053585:Virus Attachment; D053586:Virus Internalization; D018631:ras Proteins / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D036022:Capsid Proteins; D012367:RNA, Viral; C533912:CTSB protein, human; D002401:Cathepsin B; C534281:CTSL protein, human; D056668:Cathepsin L; D018631:ras Proteins
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