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Adrenomedullin (AM) and its receptor-modulating protein, RAMP2, have been identified as essential mediators of cardiovascular homeostasis. In this study, we used inducible vascular endothelial cell-specific RAMP2 knockout (DI-ERAMP22/2) mice to clarify the contribution made by the endogenous AM-RAMP2 system to angiogenesis and metastasis. Methods and resultsaEuro integral Subcutaneously transplanted sarcoma or melanoma cells showed less growth and angiogenesis in DI-E-RAMP2(-/-) than in control mice. On the other hand, after the transplantation of B16BL6 melanoma cells into hindlimb footpads, spontaneous metastasis to the lung was enhanced in DI-E-RAMP2(-/-) mice. Early after RAMP2 gene deletion, DI-E-RAMP2(-/-) mice showed enhanced vascular permeability, endothelial-mesenchymal transition (EndMT)-like change, and systemic oedema. Within the lungs of DI-E-RAMP2(-/-) mice, pulmonary endothelial cells were deformed, and inflammatory cells infiltrated the vessel walls and expressed the chemotactic factors S100A8/9 and SAA3, which attract tumour cells and mediate the formation of a pre-metastatic niche. Conversely, the overexpression of RAMP2 suppressed tumour cell adhesion to endothelial cells, tumour metastasis, and improved survival. ConclusionaEuro integral These findings indicate that the AM-RAMP2 system regulates vascular integrity, whereas RAMP2 deletion promotes vascular permeability and EndMT-like change within primary lesions and formation of pre-metastatic niches in distant organs by destabilizing the vascular structure and inducing inflammation. Vascular integrity regulated by the AM-RAMP2 system could thus be a hopeful therapeutic target for suppressing tumour metastasis."}]}, "item_1627890986942": {"attribute_name": "\u51fa\u7248\u30bf\u30a4\u30d7", "attribute_value_mlt": [{"subitem_version_resource": "http://purl.org/coar/version/c_be7fb7dd8ff6fe43", "subitem_version_type": "NA"}]}, "item_creator": {"attribute_name": "\u8457\u8005", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "\u7530\u4e2d, \u611b"}], "nameIdentifiers": [{"nameIdentifier": "103692", "nameIdentifierScheme": "WEKO"}]}]}, "item_files": {"attribute_name": "\u30d5\u30a1\u30a4\u30eb\u60c5\u5831", "attribute_type": "file", "attribute_value_mlt": [{"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2017-06-06"}], "displaytype": "detail", "download_preview_message": "", "file_order": 0, "filename": "12MH202H_shinsa.pdf", "filesize": [{"value": "97.9 kB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_note", "mimetype": "application/pdf", "size": 97900.0, "url": {"label": "\u5185\u5bb9\u306e\u8981\u65e8", "url": "https://soar-ir.repo.nii.ac.jp/record/18958/files/12MH202H_shinsa.pdf"}, "version_id": "61777b0c-279d-453f-9b99-3ff9f032a7b2"}, {"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2017-06-06"}], "displaytype": "detail", "download_preview_message": "", "file_order": 1, "filename": "12MH202H_yoshi.pdf", "filesize": [{"value": "166.8 kB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_note", "mimetype": "application/pdf", "size": 166800.0, "url": {"label": "\u5be9\u67fb\u7d50\u679c\u306e\u8981\u65e8", "url": "https://soar-ir.repo.nii.ac.jp/record/18958/files/12MH202H_yoshi.pdf"}, "version_id": "f9a1caa9-e6fe-4d86-9e44-49bec1e8b4dd"}, {"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2017-06-15"}], "displaytype": "detail", "download_preview_message": "", "file_order": 2, "filename": "12MH202H_ronbun.pdf", "filesize": [{"value": "3.6 MB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensefree": "This is a pre-copy-editing, author-produced PDF of an article accepted for publication in [Cardiovascular Research] following peer review. 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The endothelial adrenomedullin-RAMP2 system regulates vascular integrity and suppresses tumor metastasis(内皮アドレノメデュリン-RAMP2系は血管恒常性を制御し、腫瘍転移を抑制する)
http://hdl.handle.net/10091/00019720
83823ffa-39d4-427b-8ccc-1af3564f03a2
名前 / ファイル | ライセンス | アクション | |
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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公開日 | 2017-06-06 | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | The endothelial adrenomedullin-RAMP2 system regulates vascular integrity and suppresses tumor metastasis(内皮アドレノメデュリン-RAMP2系は血管恒常性を制御し、腫瘍転移を抑制する) | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源 | http://purl.org/coar/resource_type/c_db06 | |||||
タイプ | doctoral thesis | |||||
著者 |
田中, 愛
× 田中, 愛 |
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出版者 | ||||||
出版者 | 信州大学 | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 田中 愛. The endothelial adrenomedullin-RAMP2 system regulates vascular integrity and suppresses tumor metastasis(内皮アドレノメデュリン-RAMP2系は血管恒常性を制御し、腫瘍転移を抑制する). 信州大学, 2016, 博士論文. | |||||
書誌情報 |
発行日 2016-03-31 |
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学位授与番号 | ||||||
学位授与番号 | 13601甲第1061号 | |||||
学位授与年月日 | ||||||
学位授与年月日 | 2016-03-31 | |||||
学位名 | ||||||
学位名 | 博士(医学) | |||||
学位授与機関 | ||||||
学位授与機関名 | ||||||
学位授与機関名 | 信州大学(Shinshu university) | |||||
学位の区分 | ||||||
Doctoral | ||||||
学位の分野 | ||||||
医学 | ||||||
学位の報告番号 | ||||||
甲第1061号 | ||||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 雑誌に発表。CARDIOVASCULAR RESEARCH. 111(4):398-409 (2016); doi:10.1093/cvr/cvw166. | |||||
資源タイプ(コンテンツの種類) | ||||||
内容記述タイプ | Other | |||||
内容記述 | Thesis | |||||
PubMed | ||||||
関連識別子 | ||||||
識別子タイプ | PMID | |||||
関連識別子 | http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=pubmed&term=27307317 | |||||
関連名称 | ||||||
関連名称 | 27307317 | |||||
DOI | ||||||
関連識別子 | ||||||
識別子タイプ | DOI | |||||
関連識別子 | https://doi.org/10.1093/cvr/cvw166 | |||||
関連名称 | ||||||
関連名称 | 10.1093/cvr/cvw166 | |||||
権利 | ||||||
権利情報 | This is a pre-copy-editing, author-produced PDF of an article accepted for publication in [Cardiovascular Research] following peer review. The definitive publisher-authenticated version [Megumu Tanaka, Teruhide Koyama, Takayuki Sakurai, Akiko Kamiyoshi, Yuka Ichikawa-Shindo, Hisaka Kawate, Tian Liu, Xian Xian, Akira Imai, Liuyu Zhai, Kazutaka Hirabayashi, Shinji Owa, Akihiro Yamauchi, Kyoko Igarashi, Shun'ichiro Taniguchi, Takayuki Shindo; The endothelial adrenomedullin-RAMP2 system regulates vascular integrity and suppresses tumour metastasis. Cardiovasc Res 2016; 111 (4): 398-409. doi: 10.1093/cvr/cvw166] is available online at:https://doi.org/10.1093/cvr/cvw166. | |||||
出版タイプ | ||||||
出版タイプ | NA | |||||
出版タイプResource | http://purl.org/coar/version/c_be7fb7dd8ff6fe43 | |||||
WoS | ||||||
Web of Science | ||||||
URL | http://gateway.isiknowledge.com/gateway/Gateway.cgi?&GWVersion=2&SrcAuth=ShinshuUniv&SrcApp=ShinshuUniv&DestLinkType=FullRecord&DestApp=WOS&KeyUT=000383851600009 |