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The endothelial adrenomedullin-RAMP2 system regulates vascular integrity and suppresses tumor metastasis\uff08\u5185\u76ae\u30a2\u30c9\u30ec\u30ce\u30e1\u30c7\u30e5\u30ea\u30f3-RAMP2\u7cfb\u306f\u8840\u7ba1\u6052\u5e38\u6027\u3092\u5236\u5fa1\u3057\u3001\u816b\u760d\u8ee2\u79fb\u3092\u6291\u5236\u3059\u308b\uff09. \u4fe1\u5dde\u5927\u5b66, 2016, \u535a\u58eb\u8ad6\u6587.", "subitem_description_type": "Other"}]}, "item_14_dissertation_number_7": {"attribute_name": "\u5b66\u4f4d\u6388\u4e0e\u756a\u53f7", "attribute_value_mlt": [{"subitem_dissertationnumber": "13601\u7532\u7b2c1061\u53f7"}]}, "item_14_link_74": {"attribute_name": "WoS", "attribute_value_mlt": [{"subitem_link_text": "Web of Science", "subitem_link_url": "http://gateway.isiknowledge.com/gateway/Gateway.cgi?\u0026GWVersion=2\u0026SrcAuth=ShinshuUniv\u0026SrcApp=ShinshuUniv\u0026DestLinkType=FullRecord\u0026DestApp=WOS\u0026KeyUT=000383851600009"}]}, "item_14_publisher_4": {"attribute_name": "\u51fa\u7248\u8005", "attribute_value_mlt": [{"subitem_publisher": "\u4fe1\u5dde\u5927\u5b66"}]}, "item_14_relation_54": {"attribute_name": "PubMed", "attribute_value_mlt": [{"subitem_relation_name": [{"subitem_relation_name_text": "27307317"}], "subitem_relation_type_id": {"subitem_relation_type_id_text": "http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search\u0026DB=pubmed\u0026term=27307317", "subitem_relation_type_select": "PMID"}}]}, "item_14_relation_55": {"attribute_name": "DOI", "attribute_value_mlt": [{"subitem_relation_name": [{"subitem_relation_name_text": "10.1093/cvr/cvw166"}], "subitem_relation_type_id": {"subitem_relation_type_id_text": "http://dx.doi.org/10.1093/cvr/cvw166", "subitem_relation_type_select": "DOI"}}]}, "item_14_rights_69": {"attribute_name": "\u6a29\u5229", "attribute_value_mlt": [{"subitem_rights": "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\u0027ichiro 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."}]}, "item_14_select_71": {"attribute_name": "\u8457\u8005\u7248\u30d5\u30e9\u30b0", "attribute_value_mlt": [{"subitem_select_item": "ETD"}]}, "item_14_text_11": {"attribute_name": "\u5b66\u4f4d\u306e\u533a\u5206", "attribute_value_mlt": [{"subitem_text_value": "Doctoral"}]}, "item_14_text_12": {"attribute_name": "\u5b66\u4f4d\u306e\u5206\u91ce", "attribute_value_mlt": [{"subitem_text_value": "\u533b\u5b66"}]}, "item_14_text_13": {"attribute_name": "\u5b66\u4f4d\u306e\u5831\u544a\u756a\u53f7", "attribute_value_mlt": [{"subitem_text_value": "\u7532\u7b2c1061\u53f7"}]}, "item_14_text_76": {"attribute_name": "wosonly authkey", "attribute_value_mlt": [{"subitem_text_value": "Fibrosis; Macrophages; Inflammation; Vascular integrity; Endothelial cell"}]}, "item_14_text_77": {"attribute_name": "wosonly keywords", "attribute_value_mlt": [{"subitem_text_value": "MESENCHYMAL TRANSITION; LUNG METASTASIS; ANGIOGENESIS; CELLS; PEPTIDE; CANCER; INFLAMMATION; EXPRESSION; MOLECULES; ISCHEMIA"}]}, "item_14_textarea_75": {"attribute_name": "wosonly abstract", "attribute_value_mlt": [{"subitem_textarea_value": "Aims Controlling vascular integrity is expected to be a novel therapeutic target of cancers as well as cardiovascular diseases. 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_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_free", "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_free", "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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