@article{oai:kanazawa-u.repo.nii.ac.jp:00043496,
 author = {岡本, 浩一 and 田島, 秀浩 and 中村, 信一 and 牧野, 勇 and 木下, 淳 and 林, 泰寛 and 中村, 慶史 and 尾山, 勝信 and 中川原, 寿俊 and 藤田, 秀人 and 高村, 博之 and 二宮, 致 and 北川, 裕久 and 伏田, 幸夫 and 藤村, 隆 and 原田, 真市 and 若山, 友彦 and 井関, 尚一 and 太田, 哲生 and Okamoto, Koichi and Tajima, Hidehiro and Nakanuma, Shinichi and Sakai, Seisho and Makino, Isamu and Kinoshita, Jun and Hayashi, Hironori and Nakamura, Keishi and Oyama, Katsunobu and Nakagawara, Hisatoshi and Fujita, Hideto and Takamura, Hiroyuki and Ninomiya, Itasu and Kitagawa, Hirohisa and Fushida, Sachio and Fujimura, Takashi and Harada, Shinichi and Wakayama, Tomohiko and Iseki, Shoichi and Ohta, Tetsuo},
 issue = {2},
 journal = {International Journal of Oncology},
 month = {Aug},
 note = {We previously reported that hepatic stellate cells (HSCs) activated by angiotensin II (AngII) facilitate stromal fibrosis and tumor progression in intrahepatic cholangiocarcinoma (ICC). AngII has been known as a growth factor which can promote epithelial-to-mesenchymal transition (EMT) in renal epithelial cells, alveolar epithelial cells and peritoneal mesothelial cells. However, in the past, the relationship between AngII and stromal cell-derived factor-1 (SDF-1) in the microenvironment around cancer and the role of AngII on EMT of cancer cells has not been reported in detail. SDF-1 and its specific receptor, CXCR4, are now receiving attention as a mechanism of cell progression and metastasis. In this study, we examined whether activated HSCs promote tumor fibrogenesis, tumor progression and distant metastasis by mediating EMT via the AngII/AngII type 1 receptor (AT-1) and the SDF-1/CXCR4 axis. Two human ICC cell lines and a human HSC line, LI-90, express CXCR4. Significantly higher concentration of SDF-1αwas released into the supernatant of LI-90 cells to which AngII had been added. SDF-1α increased the proliferative activity of HSCs and enhanced the activation of HSCs as a growth factor. Furthermore, addition of SDF-1α and AngII enhanced the increase of the migratory capability and vimentin expression, reduced E-cadherin expression, and translocated the expression of β-catenin into the nucleus and cytoplasm in ICC cells. Co-culture with HSCs also enhanced the migratory capability of ICC cells. These findings suggest that SDF-1α, released from activated HSCs and AngII, play important roles in cancer progression, tumor fibrogenesis, and migration in autocrine and paracrine fashion by mediating EMT. Our mechanistic findings may provide pivotal insights into the molecular mechanism of the AngII and SDF-1α-initiated signaling pathway that regulates fibrogenesis in cancerous stroma, tumor progression and metastasis of tumor cells expressing AT-1 and CXCR4., Embargo Period 6 months, 金沢大学医薬保健研究域医学系},
 pages = {573--582},
 title = {Angiotensin II enhances epithelial-to-mesenchymal transition through the interaction between activated hepatic stellate cells and the stromal cell-derived factor-1/CXCR4 axis in intrahepatic cholangiocarcinoma},
 volume = {41},
 year = {2012}
}