caa a22 4500 445889012 CHVBK 20180317145609.0 cr unu---uuuuu 170323e20110501xx s 000 0 eng 10.1007/s00535-010-0345-y doi (NATIONALLICENCE)springer-10.1007/s00535-010-0345-y Downregulation of reversion-inducing-cysteine-rich protein with Kazal motifs (RECK) is associated with enhanced expression of matrix metalloproteinases and cholangiocarcinoma metastases [Elektronische Daten] [N. Namwat, J. Puetkasichonpasutha, W. Loilome, P. Yongvanit, A. Techasen, A. Puapairoj, B. Sripa, W. Tassaneeyakul, N. Khuntikeo, S. Wongkham] Background: Reversion-inducing-cysteine-rich protein with Kazal motifs (RECK) has been implicated in the attenuation of tumor metastasis by negatively regulating metalloproteinase (MMP) levels. RECK gene expression is downregulated in many solid tumors, with this downregulation being associated with poor prognosis. This study evaluated the role of RECK in cholangiocarcinoma (CCA). Methods: The expression of RECK, MMP-2, and MMP-9 in paraffin sections of hamster and human CCA specimens was analyzed by immunohistochemistry. Functional analysis of RECK was performed in RECK small interfering (si) RNA knockdown CCA cell lines. The effect of aspirin on RECK status and function was evaluated using Western blotting, gelatin zymography, invasion and proliferation assays, and PhosphoELISArray analysis of Ras downstream mediators. Results: Hamster tissues showed high RECK expression in hyperplastic biliary duct epithelia, low RECK expression in precancerous lesions, and no RECK expression in CCA. In human specimens, RECK was highly expressed in normal biliary cells, whereas intrahepatic CCA showed low levels of expression. Downregulation of RECK was correlated with tumor metastasis (P<0.01) and shorter patient survival (P<0.02). RECK expression levels were inversely correlated with MMP-2 and MMP-9 expression (P<0.05). SiRNA RECK-depleted M139 CCA cells exhibited increased MMP-2/-9 gelatinase activities and invasiveness. Aspirin (500μM) demonstrated myriad effects in human CCA cell lines, including growth suppression, reduced phosphorylation of Akt/Erk/c-Jun, elevation of RECK expression, inhibition of MMP-2/MMP-9 activity, and enhanced invasiveness. Conclusions: RECK functions as a metastasis suppressor in CCA; upregulation of RECK expression could provide a potential therapy to improve the prognosis of this type of cancer. Springer, 2010 RECK nationallicence Cholangiocarcinoma metastasis nationallicence MMP-2 nationallicence MMP-9 nationallicence Aspirin nationallicence Namwat N. Department of Biochemistry, Faculty of Medicine, Khon Kaen University, 40002, Khon Kaen, Thailand aut Puetkasichonpasutha J. Department of Biochemistry, Faculty of Medicine, Khon Kaen University, 40002, Khon Kaen, Thailand aut Loilome W. Department of Biochemistry, Faculty of Medicine, Khon Kaen University, 40002, Khon Kaen, Thailand aut Yongvanit P. Department of Biochemistry, Faculty of Medicine, Khon Kaen University, 40002, Khon Kaen, Thailand aut Techasen A. Department of Biochemistry, Faculty of Medicine, Khon Kaen University, 40002, Khon Kaen, Thailand aut Puapairoj A. Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand aut Sripa B. Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand aut Tassaneeyakul W. Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand aut Khuntikeo N. Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand aut Wongkham S. Department of Biochemistry, Faculty of Medicine, Khon Kaen University, 40002, Khon Kaen, Thailand aut Journal of Gastroenterology Springer Japan 46/5(2011-05-01), 664-675 0944-1174 46:5<664 2011 46 535 https://doi.org/10.1007/s00535-010-0345-y text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00535-010-0345-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Namwat N. Department of Biochemistry, Faculty of Medicine, Khon Kaen University, 40002, Khon Kaen, Thailand aut NATIONALLICENCE 700 1- Puetkasichonpasutha J. Department of Biochemistry, Faculty of Medicine, Khon Kaen University, 40002, Khon Kaen, Thailand aut NATIONALLICENCE 700 1- Loilome W. Department of Biochemistry, Faculty of Medicine, Khon Kaen University, 40002, Khon Kaen, Thailand aut NATIONALLICENCE 700 1- Yongvanit P. Department of Biochemistry, Faculty of Medicine, Khon Kaen University, 40002, Khon Kaen, Thailand aut NATIONALLICENCE 700 1- Techasen A. Department of Biochemistry, Faculty of Medicine, Khon Kaen University, 40002, Khon Kaen, Thailand aut NATIONALLICENCE 700 1- Puapairoj A. Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand aut NATIONALLICENCE 700 1- Sripa B. Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand aut NATIONALLICENCE 700 1- Tassaneeyakul W. Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand aut NATIONALLICENCE 700 1- Khuntikeo N. Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand aut NATIONALLICENCE 700 1- Wongkham S. Department of Biochemistry, Faculty of Medicine, Khon Kaen University, 40002, Khon Kaen, Thailand aut NATIONALLICENCE 773 0- Journal of Gastroenterology Springer Japan 46/5(2011-05-01), 664-675 0944-1174 46:5<664 2011 46 535 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer