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Loss of hepatocyte growth factor activator inhibitor type 1 participates in metastatic spreading of human pancreatic cancer cells in a mouse orthotopic transplantation model
http://hdl.handle.net/10458/4879
http://hdl.handle.net/10458/4879fb1354f6-eba4-4139-99f0-f45188166a22
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 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 | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| キーワード | HAI-1, invasion, metastasis, pancreatic cancer, PAR-2 | |||||
| 資源タイプ | ||||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| 著者 |
叶, 景佳
× 叶, 景佳× 川口, 真紀子× 春山, 幸洋× 金丸, 愛× 福島, 剛× 山本, 晃士× Lin, Chen-Yong× 片岡, 寛章 |
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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 | |||||
| 書誌情報 |
en : Cancer Science 巻 105, 号 1, p. 44-51, 発行日 2014-01 |
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| 出版者 | ||||||
| 出版者 | Japanese Cancer Association | |||||
| 言語 | en | |||||
| 出版者 | ||||||
| 出版者 | 日本癌学会 | |||||
| 言語 | ja | |||||
| DOI | ||||||
| 関連タイプ | isVersionOf | |||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | https://doi.org/10.1111/cas.12306 | |||||
| 権利 | ||||||
| 言語 | en | |||||
| 権利情報 | (C) 2013 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association. | |||||
| 他の資源との関係 | ||||||
| 関連名称 | http://hdl.handle.net/10458/4878 | |||||
