@article{oai:kanazawa-u.repo.nii.ac.jp:00043495,
 author = {中村, 信一 and 田島, 秀浩 and 岡本, 浩一 and 林, 泰寛 and 中川原, 寿俊 and 高村, 博之 and 北川, 裕久 and 伏田, 幸夫 and 谷, 卓 and 藤村, 隆 and 萱原, 正都 and 太田, 哲生 and 若山, 友彦 and 井関, 尚一 and 原田, 真市 and Nakanuma, Shinichi and Tajima, Hidehiro and Okamoto, Koichi and Hayashi, Hironori and Nakagawara, Hisatoshi and Onishi, Ichiro and Takamura, Hiroyuki and Kitagawa, Hirohisa and Fushida, Sachio and Tani, Takashi and Fujimura, Takashi and Kayahara, Masato and Ohta, Tetsuo and Wakayama, Tomohiko and Iseki, Shoichi and Harada, Shinichi},
 issue = {4},
 journal = {International Journal of Oncology},
 month = {Apr},
 note = {In primary malignant liver tumors, trypsinogen-immunoreactivity was present in 70% of intrahepatic cholangiocarcinoma (ICC) specimens, but absent in hepato-cellular carcinoma (HCC) specimens. We suggest the secretion of trypsinogen to be a key difference in biological behavior between ICC and HCC cells. The purpose of this study was to investigate the secretion of tumor-derived trypsin and the expression of its specific receptor, protease-activated receptor-2 (PAR-2), in ICC using cell lines and surgical specimens. The expression of trypsinogen-1 mRNA was observed in three of four ICC cell lines, but none of three HCC cell lines. Western blot analysis detected trypsinogen-1 in serum-free conditioned medium from one of the ICC cell lines positive for the mRNA. Gelatin zymography revealed a gelatinolytic activity for trypsin, the activated form of trypsinogen, in the same conditioned medium. PAR-2 mRNA and protein were observed in ICC cell lines. The proliferative activity of ICC cells was increased by concentrations of trypsin as low as 10 nM, and peaked at 100 nM. The effect of trypsin was suppressed by a serine protease inhibitor, gabexate mesilate. PAR-2 expression was detected in 64% of ICC surgical specimens immunohistochemically. In addition, stroma fibroblasts expressed PAR-2 in 52% of ICC specimens. These results suggest that trypsinogen-1 contributes to the growth of ICC cells and also tumor-associated fibroblasts., Embargo Period 6 months, 金沢大学医薬保健研究域医学系},
 pages = {793--800},
 title = {Tumor-derived trypsin enhances proliferation of intrahepatic cholangiocarcinoma cells by activating protease-activated receptor-2},
 volume = {36},
 year = {2010}
}