Tumor necrosis factor alpha promotes invasiveness of cholangiocarcinoma cells via its receptor, TNFR2 |
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Authors: | Tanimura Yoko Kokuryo Toshio Tsunoda Nobuyuki Yamazaki Yukiko Oda Koji Nimura Yuji Naing Mon Naing Huang Pengyu Nakanuma Yasuni Chen Min-Fu Jan Yi-Yin Yeh Ta-Sen Chiu Cheng-Taug Hsieh Ling-Ling Hamaguchi Michinari |
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Affiliation: | Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. |
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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. |
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