title: Clonorchis sinensis excretory-secretory products regulate migration and invasion in cholangiocarcinoma cells via extracellular signal-regulated kinase 1/2/nuclear factor-κB-dependent matrix metalloproteinase-9 expression.
abstract: Matrix metalloproteinase-9 plays an important role in the invasion and metastasis of various types of cancer cells. We have previously reported that excretory-secretory products from Clonorchis sinensis increases matrix metalloproteinase-9 expression. However, the regulatory mechanisms through which matrix metalloproteinase-9 expression affects cholangiocarcinoma development remain unclear. In the current study, we examined the potential role of excretory-secretory products in regulating the migration and invasion of various cholangiocarcinoma cell lines. We demonstrated that excretory-secretory products significantly induced matrix metalloproteinase-9 expression and activity in a concentration-dependent manner. Reporter gene and chromatin immunoprecipitation assays showed that excretory-secretory products induced matrix metalloproteinase-9 expression by enhancing the activity of nuclear factor-kappa B. Moreover, excretory-secretory products induced the degradation and phosphorylation of IκBα and stimulated nuclear factor-kappa B p65 nuclear translocation, which was regulated by extracellular signal-regulated kinase 1/2. Taken together, our findings indicated that the excretory-secretory product-dependent enhancement of matrix metalloproteinase-9 activity and subsequent induction of IκBα and nuclear factor-kappa B activities may contribute to the progression of cholangiocarcinoma.
authors.affiliation: Department of Convergence Medicine, University of Ulsan College of Medicine and Asan Institute for Life Sciences, Asan Medical Center, Seoul 138-736, Republic of Korea.
authors.forename: Jhang Ho
authors.initials: JH
authors.lastname: Pak
authors.affiliation: Department of Medicine, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea; Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea.
authors.forename: Jimin
authors.initials: J
authors.lastname: Shin
authors.affiliation: Department of Medicine, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea; Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea.
authors.forename: In-Sung
authors.initials: IS
authors.lastname: Song
authors.affiliation: Department of Biochemistry, Neuromarker Resource Bank, College of Natural Sciences, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Sungbo
authors.initials: S
authors.lastname: Shim
authors.affiliation: Department of Medicine, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea; Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea. Electronic address: swjang@amc.seou.kr.
authors.forename: Sung-Wuk
authors.initials: SW
authors.lastname: Jang
mesh_terms: D000818:Animals; D001650:Bile Duct Neoplasms / Q000378:metabolism / Q000469:parasitology* / Q000473:pathology; D045744:Cell Line, Tumor; D018281:Cholangiocarcinoma / Q000378:metabolism / Q000469:parasitology* / Q000473:pathology; D003003:Clonorchiasis / Q000378:metabolism*; D003004:Clonorchis sinensis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha / Q000378:metabolism; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D009362:Neoplasm Metastasis; D010766:Phosphorylation; D011817:Rabbits
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D000072000:NF-KappaB Inhibitor alpha; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Cholangiocarcinoma; Clonorchis sinensis; Excretory–secretory products; Extracellular matrix; Matrix metalloproteinase