title: Tumor necrosis factor alpha promotes invasiveness of cholangiocarcinoma cells via its receptor, TNFR2.
abstract: We studied the effect of TNF-alpha stimulation on a cholangiocarcinoma cell line, CCKS1. CCKS1 expressed only one type TNF receptor, TNFR2. Treatment of CCKS1 with TNF-alpha substantially activated NFkappaB, MAPK and Akt signalings which in turn activated matrix metalloproteinase-9 (MMP-9) secretion and in vitro invasiveness of CCKS1. Pretreatment of cells with anti-TNFR2 neutralizing antibody inhibited the TNF-alpha-dependent signaling and MMP-9 secretion and subsequently blocked invasion in vitro. Moreover, an inhibitor for matrix metalloproteinase, Galardin, suppressed the invasion in a dose-dependent manner. Similarly, pharmacological inhibition of signaling clearly suppressed the TNF-alpha dependent MMP-9 secretion. These results strongly suggest that TNF-alpha-TNFR2 signaling plays an important role to convert the cholangiocarcinoma cells to be more aggressive one.
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Tanimura
authors.forename: Toshio
authors.initials: T
authors.lastname: Kokuryo
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Tsunoda
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Yamazaki
authors.forename: Koji
authors.initials: K
authors.lastname: Oda
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nimura
authors.forename: Naing
authors.initials: N
authors.lastname: Naing Mon
authors.forename: Pengyu
authors.initials: P
authors.lastname: Huang
authors.forename: Yasuni
authors.initials: Y
authors.lastname: Nakanuma
authors.forename: Min-Fu
authors.initials: MF
authors.lastname: Chen
authors.forename: Yi-Yin
authors.initials: YY
authors.lastname: Jan
authors.forename: Ta-Sen
authors.initials: TS
authors.lastname: Yeh
authors.forename: Cheng-Taug
authors.initials: CT
authors.lastname: Chiu
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Hsieh
authors.forename: Michinari
authors.initials: M
authors.lastname: Hamaguchi
mesh_terms: D018281:Cholangiocarcinoma / Q000473:pathology*; D004789:Enzyme Activation; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D047889:Receptors, Tumor Necrosis Factor, Type II; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D020780:Matrix Metalloproteinase 9