@article{oai:kanazawa-u.repo.nii.ac.jp:00027013,
 author = {Okamoto, Koichi and Tajima, Hidehiro and Ohta, Tetsuo and Nakanuma, Shinichi and Hayashi, Hironori and Nakagawara, Hisatoshi and Onishi, Ichiro and Takamura, Hiroyuki and Ninomiya, Itasu and Kitagawa, Hirohisa and Fushida, Sachio and Tani, Takashi and Fujimura, Takashi and Kayahara, Masato and Harada, Shinichi and Wakayama, Tomohiko and Iseki, Shoichi},
 issue = {5},
 journal = {International Journal of Oncology},
 month = {Nov},
 note = {Intrahepatic cholangiocarcinoma (ICC) is characterized as a highly fatal tumor with poor prognosis because of its strong progression, early invasion, widespread metastasis and rich cancerous stroma. Although it is widely accepted that fibroblasts facilitate stromal fibrosis and tumor progression, the mechanisms of the interaction between cancer cells and activated fibroblasts have not been fully elucidated thus far. In this study, we demonstrate the presence of angiotensin II (AngII) in ICC tissues and explore the interaction between hepatic stellate cells (HSCs) and ICC cells as one of the sources of stromal fibrosis and tumor progression through the interaction of the AngII/AngII type 1 receptor (AT-1) axis. The concentrations of AngII in ICC tissues were significantly higher than those of HCC and normal liver. Two human ICC cell lines (HuCCT-1, CCKS-1) and a human HSC cell line (LI-90) expressed AT-1 mRNA and protein. The proliferative activity of ICC cells and HSCs to which AngII was added dose-dependently increased and AT-1 antagonist inhibited the proliferative effects. HSCs to which AngII was added showed a higher expression of α-smooth muscle actin (α-SMA, a marker of activated HSCs and myofibroblasts), glial fibrillary acidic protein (GFAP, a specific marker of HSCs) and collagen type I than control cells. AT-1 antagonist also inhibited the activation and transformation of HSCs stimulated by AngII. These findings suggested that locally formed AngII in ICC tissues plays a role in the proliferation and activation of ICC cells and HSCs expressing AT-1 as a growth factor in autocrine and paracrine fashions. Our mechanistic findings provide the first insight into an autocrine and paracrine AngII-initiated signaling pathway that regulates ICC proliferation and fibrosis., 富山県立中央病院, 金沢大学医薬保健研究域医学系, 金沢大学附属病院胃腸外科},
 pages = {1251--1259},
 title = {Angiotensin II induces tumor progression and fibrosis in intrahepatic cholangiocarcinoma through an interaction with hepatic stellate cells},
 volume = {37},
 year = {2010}
}