@article{oai:miyazaki-u.repo.nii.ac.jp:00001634,
 author = {叶, 景佳 and Ye, Jingjia and Kawaguchi, Makiko and 川口, 真紀子 and 春山, 幸洋 and Haruyama, Yukihiro and 金丸, 愛 and Kanemaru, Ai and Fukushima, Tsuyoshi and 福島, 剛 and Yamamoto, Koji and 山本, 晃士 and Lin, Chen-Yong and Kataoka, Hiroaki and 片岡, 寛章},
 issue = {1},
 journal = {Cancer Science},
 month = {Jan},
 note = {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.},
 pages = {44--51},
 title = {Loss of hepatocyte growth factor activator inhibitor type 1 participates in metastatic spreading of human pancreatic cancer cells in a mouse orthotopic transplantation model},
 volume = {105},
 year = {2014},
 yomi = {カワグチ, マキコ and ハルヤマ, ユキヒロ and カネマル, アイ and フクシマ, ツヨシ and ヤマモト, コウジ and カタオカ, ヒロアキ}
}