Stimulation of cultured colon 26 cells with TNF-α promotes lung metastasis through the extracellular signal-regulated kinase pathway

Choo, Min-Kyung; Sakurai, Hiroaki; Koizumi, Keiichi; Saiki, Ikuo

doi:10.1016/j.canlet.2004.12.027

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Volume 230, Issue 1 , Pages 47-56, 8 December 2005

Stimulation of cultured colon 26 cells with TNF-α promotes lung metastasis through the extracellular signal-regulated kinase pathway

Min-Kyung Choo
- Division of Pathogenic Biochemistry, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan
Hiroaki Sakurai
- Division of Pathogenic Biochemistry, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan
- 21st Century COE Program, Toyama Medical and Pharmaceutical University, Toyama 930-0194, Japan
- Corresponding author. Address: Division of Pathogenic Biochemistry, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan. Tel.: +81 76 434 7636; fax: +81 76 434 5058.
Keiichi Koizumi
- Division of Pathogenic Biochemistry, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan
Ikuo Saiki
- Division of Pathogenic Biochemistry, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan
- 21st Century COE Program, Toyama Medical and Pharmaceutical University, Toyama 930-0194, Japan

Received 26 November 2004; received in revised form 15 December 2004; accepted 15 December 2004.

Abstract

We investigated the influence of TNF-α on the metastasis of cancer cells. Treatment of cultured colon 26 cells with TNF-α enhanced metastatic properties including production of MMP-9, adhesion, migration and invasion. Cells treated with TNF-α in vitro showed marked potential to metastasize to the lung and liver in vivo. U0126, an inhibitor of MEK1/2, inhibited the TNF-α-induced activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and the metastatic properties in vitro without affecting cell proliferation. In addition, pretreatment with U0126 in vitro completely abrogated the increased lung metastasis of TNF-α-treated cells. These results indicate that TNF-α-induced activation of cancer cells through the ERK pathway is sufficient for the enhanced metastatic potential of colon 26 cells.

Keywords: Tumor necrosis factor-α, Metastasis, Extracellular signal-regulated kinase, Matrix metalloproteinase-9

Abbreviations: TNF, tumor necrosis factor, MAPK, mitogen-activated protein kinase, ERK, extracellular signal-regulated kinase, MEK, MAPK/extracellular signal-regulated kinase, MMP, matrix metalloproteinase