Fascin is involved in tumor necrosis factor-alpha-dependent production of MMP9 in cholangiocarcinoma.

Abstract

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.

• Authors: Manabu Onodera, Yoh Zen, Kenichi Harada, Yasunori Sato, Hiroko Ikeda, Keita Itatsu, Hiroshi Sato, Tetsuo Ohta, Masahiro Asaka, Yasuni Nakanuma
• Journal: Laboratory investigation; a journal of technical methods and pathology (Lab Invest) Vol. 89 Issue 11 Pg. 1261-74 (Nov 2009) ISSN: 1530-0307 [Electronic] United States
• PMID: 19721413 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• Carrier Proteins
• Microfilament Proteins
• RNA, Messenger
• RNA, Small Interfering
• Tumor Necrosis Factor-alpha
• fascin
• Matrix Metalloproteinase 9

Topics

• Adult
• Aged
• Aged, 80 and over
• Bile Duct Neoplasms (enzymology, physiopathology)
• Bile Ducts, Intrahepatic (enzymology, physiopathology)
• Biliary Tract (enzymology, pathology)
• Biomarkers, Tumor (metabolism)
• 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 Necrosis Factor-alpha (metabolism, pharmacology)