{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1360004236376464000.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1158/1541-7786.mcr-18-0321"}},{"identifier":{"@type":"URI","@value":"https://aacrjournals.org/mcr/article-pdf/16/11/1676/2313471/1676.pdf"}},{"identifier":{"@type":"PMID","@value":"30042177"}}],"resourceType":"学術雑誌論文(journal article)","dc:title":[{"@value":"Radiation-Induced Myofibroblasts Promote Tumor Growth via Mitochondrial ROS–Activated TGFβ Signaling"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:title>Abstract</jats:title>\n                  <jats:p>Fibroblasts are a key stromal cell in the tumor microenvironment (TME) and promote tumor growth via release of various growth factors. Stromal fibroblasts in cancer, called cancer-associated fibroblasts (CAF), are related to myofibroblasts, an activated form of fibroblast. While investigating the role of stroma fibroblasts on radiation-related carcinogenesis, it was observed following long-term fractionated radiation (FR) that the morphology of human diploid fibroblasts changed from smaller spindle shapes to larger flat shapes. These cells expressed smooth muscle actin (α-SMA) and platelet-derived growth factor receptors, markers of myofibroblasts and CAFs, respectively. Long-term FR induces progressive damage to the fibroblast nucleus and mitochondria via increases in mitochondrial reactive oxygen species (ROS) levels. Here, it is demonstrated that long-term FR-induced α-SMA–positive cells have decreased mitochondrial membrane potential and activated oxidative stress responses. Antioxidant N-acetyl cysteine suppressed radiation-induced mitochondrial damage and generation of myofibroblasts. These results indicate that mitochondrial ROS are associated with the acquisition of myofibroblasts after long-term FR. Mechanistically, mitochondrial ROS activated TGFβ signaling which in turn mediated the expression of α-SMA in radiation-induced myofibroblasts. Finally, in vivo tumor growth analysis in a human tumor xenograft model system revealed that long-term FR-induced myofibroblasts promote tumor growth by enhancing angiogenesis.</jats:p>\n                  <jats:p>Implications: Radiation affects malignant cancer cells directly and indirectly via molecular alterations in stromal fibroblasts such as activation of TGFβ and angiogenic signaling pathways. Mol Cancer Res; 16(11); 1676–86. ©2018 AACR.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1420845751139752064","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"40463799"},{"@type":"NRID","@value":"1000040463799"},{"@type":"NRID","@value":"9000392723495"},{"@type":"NRID","@value":"9000020747110"},{"@type":"NRID","@value":"9000412406566"},{"@type":"NRID","@value":"9000391985335"},{"@type":"NRID","@value":"9000283193795"},{"@type":"NRID","@value":"9000009084705"},{"@type":"NRID","@value":"9000067031320"},{"@type":"NRID","@value":"9000387916478"},{"@type":"NRID","@value":"9000307265199"},{"@type":"NRID","@value":"9000391987560"},{"@type":"NRID","@value":"9000317127651"},{"@type":"NRID","@value":"9000367832604"},{"@type":"NRID","@value":"9000347049891"},{"@type":"NRID","@value":"9000414070415"},{"@type":"NRID","@value":"9000258167477"},{"@type":"NRID","@value":"9000107382403"},{"@type":"NRID","@value":"9000329440436"},{"@type":"NRID","@value":"9000356673227"},{"@type":"NRID","@value":"9000401741126"},{"@type":"NRID","@value":"9000391976519"},{"@type":"NRID","@value":"9000391983958"},{"@type":"NRID","@value":"9000391977262"},{"@type":"NRID","@value":"9000387916489"},{"@type":"NRID","@value":"9000347050485"},{"@type":"NRID","@value":"9000258170819"},{"@type":"NRID","@value":"9000356514026"},{"@type":"NRID","@value":"9000391980830"},{"@type":"NRID","@value":"9000367833007"},{"@type":"NRID","@value":"9000391979182"},{"@type":"NRID","@value":"9000391981530"},{"@type":"NRID","@value":"9000411260066"},{"@type":"NRID","@value":"9000258171660"},{"@type":"NRID","@value":"9000387916525"},{"@type":"NRID","@value":"9000401745406"},{"@type":"NRID","@value":"9000391982181"},{"@type":"NRID","@value":"9000107356313"},{"@type":"NRID","@value":"9000018767929"},{"@type":"NRID","@value":"9000356514012"},{"@type":"NRID","@value":"9000387916509"},{"@type":"NRID","@value":"9000391987206"},{"@type":"NRID","@value":"9000241623400"},{"@type":"NRID","@value":"9000401731577"},{"@type":"NRID","@value":"9000107346242"},{"@type":"NRID","@value":"9000347049262"},{"@type":"NRID","@value":"9000401618960"},{"@type":"NRID","@value":"9000401715804"},{"@type":"NRID","@value":"9000297499392"},{"@type":"NRID","@value":"9000347050246"},{"@type":"NRID","@value":"9000391986986"},{"@type":"NRID","@value":"9000391987671"},{"@type":"NRID","@value":"9000356514019"},{"@type":"NRID","@value":"9000397827020"},{"@type":"NRID","@value":"9000387916522"},{"@type":"NRID","@value":"9000401733236"},{"@type":"NRID","@value":"9000391983495"},{"@type":"ORCID","@value":"0000-0002-2418-2991"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/sal"}],"foaf:name":[{"@value":"Tsutomu 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