| Fascin is involved in tumor necrosis factor-alpha-dependent production of MMP9 in cholangiocarcinoma. | |
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MedLine Citation:
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PMID: 19721413 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Fascin is an actin-binding protein involved in the cell motility. Recently, aberrant expression of fascin in carcinoma cells was reported to participate in their invasive growth in cooperation with proteinases such as matrix metalloproteinases (MMPs). This study examined the participation of fascin in the progression of cholangiocarcinoma (CC) with reference to MMPs and tumor necrosis factor-alpha (TNF-alpha). Expression levels of fascin and MMP2 and 9 were examined immunohistochemically in human non-neoplastic biliary epithelium (13 cases) and CC (87 cases). The relationship between fascin and MMP9-expression levels was examined using two CC cell lines (CCKS-1 and HuCCT1). It was also examined whether or not fascin was involved in TNF-alpha-induced overproduction of MMP9 in CC. Fascin and MMP9 were expressed in 49 and 53% of CC samples, respectively, and the expression of these genes was frequent in intrahepatic CC. Fascin expression was correlated significantly with MMP9 expression. In particular, these two molecules were expressed more intensely at the invasive fronts of CC. Fascin expression was an unfavorable prognostic factor for patients with intrahepatic CC. In vitro studies showed that TNF-alpha could induce the overexpression of fascin and MMP9 in two CC cell lines. A knockdown study of fascin by siRNA showed that TNF-alpha induced the overproduction of fascin, which in turn upregulated MMP9 expression. Overexpression of fascin may have an important function in the progression of CC, and fascin expression might be involved in the signaling pathway in TNF-alpha-dependent production of MMP9 in CC. |
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Authors:
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Manabu Onodera; Yoh Zen; Kenichi Harada; Yasunori Sato; Hiroko Ikeda; Keita Itatsu; Hiroshi Sato; Tetsuo Ohta; Masahiro Asaka; Yasuni Nakanuma |
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Publication Detail:
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Type: Journal Article Date: 2009-08-31 |
Journal Detail:
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Title: Laboratory investigation; a journal of technical methods and pathology Volume: 89 ISSN: 1530-0307 ISO Abbreviation: Lab. Invest. Publication Date: 2009 Nov |
Date Detail:
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Created Date: 2009-10-28 Completed Date: 2009-11-12 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0376617 Medline TA: Lab Invest Country: United States |
Other Details:
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Languages: eng Pagination: 1261-74 Citation Subset: IM |
Affiliation:
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Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Aged, 80 and over Bile Duct Neoplasms / enzymology*, physiopathology Bile Ducts, Intrahepatic / enzymology*, physiopathology Biliary Tract / enzymology, pathology Carrier Proteins / physiology* Cell Count Cell Line, Tumor Cholangiocarcinoma / enzymology*, physiopathology Disease Progression Epithelial Cells / enzymology, pathology Female Fluorescent Antibody Technique, Direct Gene Expression Regulation, Neoplastic / drug effects Gene Silencing Humans Immunoenzyme Techniques Male Matrix Metalloproteinase 9 / biosynthesis*, genetics Microfilament Proteins / physiology* Middle Aged RNA, Messenger / genetics RNA, Small Interfering / genetics Transfection Tumor Cells, Cultured Tumor Markers, Biological / metabolism Tumor Necrosis Factor-alpha / metabolism*, pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Carrier Proteins; 0/Microfilament Proteins; 0/RNA, Messenger; 0/RNA, Small Interfering; 0/Tumor Markers, Biological; 0/Tumor Necrosis Factor-alpha; 146808-54-0/fascin; EC 3.4.24.35/Matrix Metalloproteinase 9 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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