Activity levels of cathepsins B and L in tumor cells are a biomarker for efficacy of reovirus-mediated tumor cell killing
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 factor...
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| Veröffentlicht in: | Cancer gene therapy 2015-04, Vol.22 (4), p.188-197 |
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| creator | Terasawa, Y Hotani, T Katayama, Y Tachibana, M Mizuguchi, H Sakurai, F |
| description | 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. |
| doi_str_mv | 10.1038/cgt.2015.4 |
| format | Article |
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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.</description><identifier>ISSN: 0929-1903</identifier><identifier>EISSN: 1476-5500</identifier><identifier>DOI: 10.1038/cgt.2015.4</identifier><identifier>PMID: 25633482</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>631/67/1059/602 ; Analysis ; Animals ; Apoptosis ; Biomarkers ; Biomarkers, Tumor - metabolism ; Biomedical and Life Sciences ; Biomedicine ; Cancer ; Cancer treatment ; Capsid Proteins - metabolism ; Care and treatment ; Cathepsin B - metabolism ; Cathepsin L - metabolism ; Cathepsins ; Cell activation ; Cell Survival ; Cysteine ; Cystine ; Diagnosis ; Enzyme Activation ; Gene Expression ; Gene Therapy ; Genetic aspects ; HEK293 Cells ; Hep G2 Cells ; Humans ; Immunity, Innate ; MCF-7 Cells ; Mice ; Oncolysis ; original-article ; Orthoreovirus, Mammalian - immunology ; Orthoreovirus, Mammalian - physiology ; Proteases ; Proteins ; Proteolysis ; ras Proteins - metabolism ; Reovirus ; Reoviruses ; Replication ; RNA polymerases ; RNA, Viral - genetics ; RNA, Viral - metabolism ; Tumor cells ; Tumors ; Viral proteins ; Virus Attachment ; Virus Internalization</subject><ispartof>Cancer gene therapy, 2015-04, Vol.22 (4), p.188-197</ispartof><rights>Nature America, Inc. 2015</rights><rights>COPYRIGHT 2015 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Apr 2015</rights><rights>Nature America, Inc. 2015.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c643t-9bdce611ff4184eb44c787c3c930c2f7a9a417e2fd7d4dc02433441ffd74a5233</citedby><cites>FETCH-LOGICAL-c643t-9bdce611ff4184eb44c787c3c930c2f7a9a417e2fd7d4dc02433441ffd74a5233</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/cgt.2015.4$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/cgt.2015.4$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,777,781,27905,27906,41469,42538,51300</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25633482$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Terasawa, Y</creatorcontrib><creatorcontrib>Hotani, T</creatorcontrib><creatorcontrib>Katayama, Y</creatorcontrib><creatorcontrib>Tachibana, M</creatorcontrib><creatorcontrib>Mizuguchi, H</creatorcontrib><creatorcontrib>Sakurai, F</creatorcontrib><title>Activity levels of cathepsins B and L in tumor cells are a biomarker for efficacy of reovirus-mediated tumor cell killing</title><title>Cancer gene therapy</title><addtitle>Cancer Gene Ther</addtitle><addtitle>Cancer Gene Ther</addtitle><description>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.</description><subject>631/67/1059/602</subject><subject>Analysis</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer</subject><subject>Cancer treatment</subject><subject>Capsid Proteins - metabolism</subject><subject>Care and treatment</subject><subject>Cathepsin B - metabolism</subject><subject>Cathepsin L - metabolism</subject><subject>Cathepsins</subject><subject>Cell activation</subject><subject>Cell Survival</subject><subject>Cysteine</subject><subject>Cystine</subject><subject>Diagnosis</subject><subject>Enzyme Activation</subject><subject>Gene Expression</subject><subject>Gene Therapy</subject><subject>Genetic aspects</subject><subject>HEK293 Cells</subject><subject>Hep G2 Cells</subject><subject>Humans</subject><subject>Immunity, Innate</subject><subject>MCF-7 Cells</subject><subject>Mice</subject><subject>Oncolysis</subject><subject>original-article</subject><subject>Orthoreovirus, Mammalian - 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Academic</collection><collection>Biotechnology Research Abstracts</collection><jtitle>Cancer gene therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Terasawa, Y</au><au>Hotani, T</au><au>Katayama, Y</au><au>Tachibana, M</au><au>Mizuguchi, H</au><au>Sakurai, F</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Activity levels of cathepsins B and L in tumor cells are a biomarker for efficacy of reovirus-mediated tumor cell killing</atitle><jtitle>Cancer gene therapy</jtitle><stitle>Cancer Gene Ther</stitle><addtitle>Cancer Gene Ther</addtitle><date>2015-04-01</date><risdate>2015</risdate><volume>22</volume><issue>4</issue><spage>188</spage><epage>197</epage><pages>188-197</pages><issn>0929-1903</issn><eissn>1476-5500</eissn><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. 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| ispartof | Cancer gene therapy, 2015-04, Vol.22 (4), p.188-197 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; SpringerLink Journals - AutoHoldings |
| subjects | 631/67/1059/602 Analysis Animals Apoptosis Biomarkers Biomarkers, Tumor - metabolism Biomedical and Life Sciences Biomedicine Cancer Cancer treatment Capsid Proteins - metabolism Care and treatment Cathepsin B - metabolism Cathepsin L - metabolism Cathepsins Cell activation Cell Survival Cysteine Cystine Diagnosis Enzyme Activation Gene Expression Gene Therapy Genetic aspects HEK293 Cells Hep G2 Cells Humans Immunity, Innate MCF-7 Cells Mice Oncolysis original-article Orthoreovirus, Mammalian - immunology Orthoreovirus, Mammalian - physiology Proteases Proteins Proteolysis ras Proteins - metabolism Reovirus Reoviruses Replication RNA polymerases RNA, Viral - genetics RNA, Viral - metabolism Tumor cells Tumors Viral proteins Virus Attachment Virus Internalization |
| title | Activity levels of cathepsins B and L in tumor cells are a biomarker for efficacy of reovirus-mediated tumor cell killing |
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