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

Cancer Lett. 2005 Dec 8;230(1):47-56. doi: 10.1016/j.canlet.2004.12.027.

Abstract

We investigated the influence of TNF-alpha on the metastasis of cancer cells. Treatment of cultured colon 26 cells with TNF-alpha enhanced metastatic properties including production of MMP-9, adhesion, migration and invasion. Cells treated with TNF-alpha in vitro showed marked potential to metastasize to the lung and liver in vivo. U0126, an inhibitor of MEK1/2, inhibited the TNF-alpha-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-alpha-treated cells. These results indicate that TNF-alpha-induced activation of cancer cells through the ERK pathway is sufficient for the enhanced metastatic potential of colon 26 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion
  • Cell Movement
  • Colonic Neoplasms / pathology*
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Female
  • Humans
  • Lung Neoplasms / physiopathology*
  • Lung Neoplasms / secondary*
  • Matrix Metalloproteinase 9 / biosynthesis
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Invasiveness
  • Neoplasm Metastasis / physiopathology*
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / physiology*

Substances

  • Tumor Necrosis Factor-alpha
  • Extracellular Signal-Regulated MAP Kinases
  • Matrix Metalloproteinase 9