{"created":"2023-07-27T06:44:32.087015+00:00","id":34793,"links":{},"metadata":{"_buckets":{"deposit":"59c56966-894c-46f1-90cf-8c6f1dca8cbe"},"_deposit":{"created_by":3,"id":"34793","owners":[3],"pid":{"revision_id":0,"type":"depid","value":"34793"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00034793","sets":["2812:2813:2830"]},"author_link":["23232","9956"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2004-03-01","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"5p.","bibliographicVolumeNumber":"2002-2003","bibliographic_titles":[{"bibliographic_title":"平成15(2003)年度 科学研究費補助金 基盤研究(B) 研究成果報告書"},{"bibliographic_title":"2003 Fiscal Year Final Research Report","bibliographic_titleLang":"en"}]}]},"item_9_creator_33":{"attribute_name":"著者別表示","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{}],"nameIdentifiers":[{},{}]}]},"item_9_description_21":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"膜型マトリックスメタロプロテアーゼMT1-MMPは癌細胞表面に特異的に発現し癌の浸潤・転移に重要な役割を果たすと考えられるが、その機能については不明な点が多く、また従来の生化学的なアプローチではその解明は困難であった。我々はMT1-MMPの制御因子及び新規基質を同定する発現クローニング法を開発し、いくつかの分子を同定し、癌の浸潤・転移における機能を明らかにした。例えば、シンデカンー1の発現レベルは癌の悪性度と逆相関することが知られているが、我々はシンデカンー1の発現はコラーゲン上での細胞運動を抑制し、MT-MMPによりシンデカンー1の細胞外ドメインが切断されたことにより運動性が亢進することを明らかにした。さらにMT-MMPの新規基質として癌転移抑制遺伝子産物KiSS-1を同定した。またMT-MMPはKiSS-1遺伝子にコードされるmetastinペプチドをも分解することを明らかにした。metastinはGタンパク共役型受容体と結合して細胞運動を負に制御することにより癌転移を抑制することが報告されているが、本研究では癌細胞の発現するMMPによりmetastinが分解されることを見い出し、MMP阻害剤とmetastinの併用は効率良く癌細胞の運動を抑制することを報告した。本研究で明かとなったMT1-MMPの新規機能は今後、MT1-MMPを分子標的とした癌治療法を開発する上で重要な知見となる。","subitem_description_type":"Abstract"},{"subitem_description":"Membrane-type matrix metalloproteinase(MT1-MMP) is expressed on the surface of tumor cells, and thought to play an important role in tumor invasion and metastasis. However, the functions of MT1-MMP still remain unsolved, and would not be investigated by classical biochemical approach. We have developed a novel expression cloning method to screen molecules, which either regulate MT1-MMP activity or serve as substrates for it, and identified several molecules. For example, syndecan-1, expression of which is known to have reverse co-relation with the malignancy of tumors, was demonstrated to be cleaved to shed the ecto-domain. Expression of syndecan-1 was shown to suppress cell migration on collagen, which was abrogated by the cleavage of syndecan-1 by MT1-MMP. Furthermore, we identified metastasis suppressor gene product KiSS-1 protein as a substrate for MMP. Metastin peptide encoded by KiSS-1 gene was also shown to be cleaved by MMP. Metastin is known to repress cell migration by binding to the G-protein-coupled receptor(GPCR). Since metastin is inactivated by MMPs produced by tumor cells, migration of tumor cells expressing GPCR could be suppressed by co-treatment with metastin and MMP inhibitor. These results suggest that study on functions of MT1-MMP may contribute to the development of novel therapy targeting MT1-MMP.","subitem_description_type":"Abstract"}]},"item_9_description_22":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"研究課題/領域番号:14370053, 研究期間(年度):2002–2003","subitem_description_type":"Other"},{"subitem_description":"出典：「癌転移における膜型マトリックスメタロプロテアーゼの新規機能の解析」研究成果報告書　課題番号14370053\n  (KAKEN：科学研究費助成事業データベース（国立情報学研究所）)\n　　　本文データは著者版報告書より作成","subitem_description_type":"Other"}]},"item_9_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00034780","subitem_identifier_reg_type":"JaLC"}]},"item_9_publisher_17":{"attribute_name":"公開者","attribute_value_mlt":[{"subitem_publisher":"金沢大学がん研究所"}]},"item_9_relation_28":{"attribute_name":"関連URI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/search/?qm=00115239","subitem_relation_type_select":"URI"}},{"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-14370053/","subitem_relation_type_select":"URI"}},{"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-14370053/143700532003kenkyu_seika_hokoku_gaiyo/","subitem_relation_type_select":"URI"}}]},"item_9_version_type_25":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_ab4af688f83e57aa","subitem_version_type":"AM"}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2017-10-05"}],"displaytype":"detail","filename":"CA-PR-SATO-H-kaken 2004-5p.pdf","filesize":[{"value":"220.7 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"CA-PR-SATO-H-kaken 2004-5p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/34793/files/CA-PR-SATO-H-kaken 2004-5p.pdf"},"version_id":"84626c7c-a78a-4542-8072-ca965e96e358"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"research report","resourceuri":"http://purl.org/coar/resource_type/c_18ws"}]},"item_title":"癌転移における膜型マトリックスメタロプロテアーゼの新規機能の解析","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"癌転移における膜型マトリックスメタロプロテアーゼの新規機能の解析"},{"subitem_title":"Study on novel functions of membrane-type matrix metalloproteinase in tumor metastasis","subitem_title_language":"en"}]},"item_type_id":"9","owner":"3","path":["2830"],"pubdate":{"attribute_name":"公開日","attribute_value":"2017-10-05"},"publish_date":"2017-10-05","publish_status":"0","recid":"34793","relation_version_is_last":true,"title":["癌転移における膜型マトリックスメタロプロテアーゼの新規機能の解析"],"weko_creator_id":"3","weko_shared_id":3},"updated":"2023-07-27T14:36:19.421260+00:00"}