| Angiotensin II induces tumor progression and fibrosis in intrahepatic cholangiocarcinoma through an interaction with hepatic stellate cells. | |
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MedLine Citation:
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PMID: 20878072 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Koichi Okamoto; Hidehiro Tajima; Tetsuo Ohta; Shinichi Nakanuma; Hironori Hayashi; Hisatoshi Nakagawara; Ichiro Onishi; Hiroyuki Takamura; Itasu Ninomiya; Hirohisa Kitagawa; Sachio Fushida; Takashi Tani; Takashi Fujimura; Masato Kayahara; Shinichi Harada; Tomohiko Wakayama; Shoichi Iseki |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: International journal of oncology Volume: 37 ISSN: 1791-2423 ISO Abbreviation: Int. J. Oncol. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-09-29 Completed Date: 2011-01-25 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9306042 Medline TA: Int J Oncol Country: Greece |
Other Details:
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Languages: eng Pagination: 1251-9 Citation Subset: IM |
Affiliation:
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Gastroenterologic Surgery, Department of Oncology, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8640, Japan. kookka5151@gmail.com |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Angiotensin II
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metabolism* Bile Duct Neoplasms / metabolism*, pathology Bile Ducts, Intrahepatic / metabolism*, pathology Blotting, Western Cholangiocarcinoma / metabolism*, pathology Disease Progression Fibrosis Glial Fibrillary Acidic Protein / biosynthesis Hepatic Stellate Cells / metabolism* Humans Immunohistochemistry Membrane Transport Proteins / biosynthesis Reverse Transcriptase Polymerase Chain Reaction Signal Transduction / physiology |
| Chemical | |
Reg. No./Substance:
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0/Glial Fibrillary Acidic Protein; 0/Membrane Transport Proteins; 0/SLC33A1 protein, human; 11128-99-7/Angiotensin II |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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