Stimulation of cultured colon 26 cells with TNF-alpha promotes lung metastasis through the extracellular signal-regulated kinase pathway.
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.
Choo
Min-Kyung
MK
Division of Pathogenic Biochemistry, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.
Sakurai
Hiroaki
H
Koizumi
Keiichi
K
Saiki
Ikuo
I
D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D003110:Colonic Neoplasms / Q000473:pathology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000503:physiopathology* / Q000556:secondary*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D014409:Tumor Necrosis Factor-alpha; D048049:Extracellular Signal-Regulated MAP Kinases; D020780:Matrix Metalloproteinase 9