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

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.