Tumor necrosis factor α promotes invasiveness of cholangiocarcinoma cells via its receptor, TNFR2

被引：48

作者：

Tanimura, Y

Kokuryo, T

Tsunoda, N

Yamazaki, Y

Oda, K

Nimura, Y

Mon, NN

Huang, PY

Nakanuma, Y

Chen, MF

Jan, YY

Yeh, TS

Chiu, CT

Hsieh, LL

Hamaguchi, M

机构：

[1] Nagoya Univ, Grad Sch Med, Div Canc Biol, Showa Ku, Nagoya, Aichi 4668550, Japan

[2] Nagoya Univ, Grad Sch Med, Dept Surg, Div Surg Oncol,Showa Ku, Nagoya, Aichi 4668550, Japan

[3] Kanazawa Univ, Grad Sch Med, Dept Human Pathol, Kanazawa, Ishikawa 9208641, Japan

[4] Chang Gumg Univ, Mem Hosp, Dept Surg, Taipei 105, Taiwan

[5] Chang Gumg Univ, Mem Hosp, Dept Gastroenterol, Taipei 105, Taiwan

[6] Chang Gumg Univ, Mem Hosp, Dept Publ Hlth, Taipei 105, Taiwan

来源：

CANCER LETTERS | 2005年 / 219卷 / 02期

关键词：

cholangiocarcinoma; matrix metalloproteinase; tumor necrosis factor-alpha; invasion;

D O I：

10.1016/j.canlet.2004.07.027

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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-a substantially activated NF kappa B, 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. (c) 2004 Elsevier Ireland Ltd. All rights reserved.

引用

页码：205 / 213

页数：9

共 32 条

[1]

Amin ARMR, 2003, CANCER RES, V63, P6334

[2] Secretion of matrix metalloproteinase-9 by the proinflammatory cytokine, IL-1β:: a role for the dual signalling pathways, Akt and Erk [J].