Chondrosarcoma is a type of highly malignant tumour with a potent capacity to invade locally and cause distant metastasis. Chondrosarcoma shows a predilection for metastasis to the lungs. Tumour necrosis factor (TNF)-α is a key cytokine involved in inflammation, immunity, cellular homeostasis and tumour progression. Integrins are the major adhesive molecules in mammalian cells and have been associated with metastasis of cancer cells. However, the effects of TNF-α in migration and integrin expression in chondrosarcoma cells are largely unknown. In this study, we found that TNF-α increased the migration and the expression of αvβ3 integrin in human chondrosarcoma cells. Activations of MAPK kinase (MEK), extracellular signal-regulating kinase (ERK) and nuclear factor-κB (NF-κB) pathways after TNF-α treatment were demonstrated, and TNF-α-induced expression of integrin and migration activity was inhibited by the specific inhibitor and mutant of MEK, ERK and NF-κB cascades. Taken together, our results indicated that TNF-α enhances the migration of chondrosarcoma cells by increasing αvβ3 integrin expression through the MEK/ERK/NF-κB signal transduction pathway.
Copyright © 2010 Wiley-Liss, Inc.