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HAI-1発現低下はヒト膵癌細胞のマウス同所移植モデルにおける転移巣形成に関与している
http://hdl.handle.net/10458/4878
http://hdl.handle.net/10458/487835bff775-6c81-4f23-be21-1c45102714cb
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論文要旨 (77.7 kB)
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学位論文審査結果の要旨 (71.3 kB)
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博士学位論文 (1.9 MB)
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| アイテムタイプ | 学位論文 / Thesis or Dissertation(1) | |||||
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| 公開日 | 2014-06-10 | |||||
| タイトル | ||||||
| タイトル | Loss of hepatocyte growth factor activator inhibitor type 1 participates in metastatic spreading of human pancreatic cancer cells in a mouse orthotopic transplantation model | |||||
| 言語 | en | |||||
| タイトル | ||||||
| タイトル | HAI-1発現低下はヒト膵癌細胞のマウス同所移植モデルにおける転移巣形成に関与している | |||||
| 言語 | ja | |||||
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| 言語 | eng | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | HAI-1, invasion, metastasis, pancreatic cancer, PAR-2 | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||
| 資源タイプ | doctoral thesis | |||||
| アクセス権 | ||||||
| アクセス権 | open access | |||||
| 著者 |
叶, 景佳
× 叶, 景佳 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Hepatocyte growth factor activator inhibitor type 1 (HAI-1) is a membrane-bound serine protease inhibitor that is expressed on the surface of epithelial and carcinoma cells. On the cell surface, HAI-1 regulates membrane-anchored serine proteases, with matriptase being the most critical target. Matriptase is involved in pericellular processing of biologically active molecules, including proteaseactivated receptor-2 (PAR-2). Previously we reported that S2-CP8 cells, a metastatic variant of the SUIT-2 human pancreatic adenocarcinoma cell line, showed markedly decreased HAI-1 expression. To assess the significance of HAI-1 loss in invasion and spontaneous metastasis of S2-CP8 cells, we established stable S2-CP8 sublines that expressed HAI-1 under the control of a tetracycline-regulated promoter. In vitro migration and invasion assays revealed inhibitory effects of HAI-1 on S2-CP8 cell migration and invasion. Matriptase activity was suppressed by the expression of HAI-1. As the enhanced invasiveness in the absence of HAI-1 was alleviated by knockdown of matriptase by 81% and of PAR-2 completely, and PAR-2 antagonist also suppressed the invasion, matriptase-mediated PAR-2 activation is involved in HAI-1 loss-induced invasion of S2-CP8 cells. We then analyzed the effect of HAI-1 expression on metastasis of S2-CP8 cells in vivo using a nude mouse orthotopic xenograft model. Although approximately 50% of the control mice developed distant metastasis, mice treated with doxycycline to induce HAI-1 expression did not develop metastasis. These data indicate that HAI-1 loss contributes to invasion and dissemination of a highly metastatic subline of SUIT-2, suggesting crucial roles for the balance of pericellular serine proteases/inhibitors in pancreatic cancer progression. | |||||
| 言語 | en | |||||
| 内容記述 | ||||||
| 言語 | ja | |||||
| 値 | 本論文に関連する研究論文 Ye J, Kawaguchi M, Haruyama Y, Kanemaru A, Fukushima T, Yamamoto K, Lin CY, Kataoka H. Loss of hepatocyte growth factor activator inhibitor type 1 participates in metastatic spreading of human pancreatic cancer cells in a mouse orthotopic transplantation model. Cancer Sci. 2014 Jan;105(1):44-51. doi: 10.1111/cas.12306. Epub 2013 Nov 25. PMID: 24147538; PMCID: PMC4317873. |
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| 学位名 | ||||||
| 学位名 | 博士(医学) | |||||
| 言語 | ja | |||||
| 学位授与機関 | ||||||
| 学位授与機関識別子Scheme | kakenhi | |||||
| 学位授与機関識別子 | 17601 | |||||
| 学位授与機関名 | 宮崎大学 | |||||
| 言語 | ja | |||||
| 学位授与年度 | ||||||
| 内容記述 | 2014年度 | |||||
| 言語 | ja | |||||
| 学位授与年月日 | ||||||
| 学位授与年月日 | 2014-04-30 | |||||
| 学位授与番号 | ||||||
| 学位授与番号 | 医博乙第51号 | |||||
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| 関連名称 | http://hdl.handle.net/10458/4879 | |||||
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| 出版タイプ | VoR | |||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
| リンク |
Loss of hepatocyte growth factor activator inhibitor type 1 participates in metastatic spreading of human pancreatic cancer cells in a mouse orthotopic transplantation model
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