Antioxidants inhibit TNFα-induced motility and invasion of human osteosarcoma cells: Possible involvement of NFκB activation

Osteosarcoma is the most frequent malignant bone tumor in children. It is highly invasive, however, the mechanisms behind osteosarcoma cell invasion are as yet still unknown. In the present study, treatment with TNFα enhanced the invasiveness of two human osteosarcoma cell lines, OST and MNNG. TNFα treatment also induced tumor cell motility, adhesion to laminin, the expression of matrix metalloproteinase 9 (MMP9), and the nuclear translocation of nuclear factor κB (NFκB) in the osteosarcoma cells. Moreover, antioxidants inhibited TNFα-induced osteosarcoma cell invasion, motility and NFκB nuclear translocation, but not adhesion to laminin or MMP9 expression. NFκB decoy, another NFκB inhibitor, also inhibited TNFα-induced osteosarcoma cell invasion and motility. Therefore, motility and NFκB activation were possibly related to TNFα-induced osteosarcoma cell invasion. However, adhesion to laminin or MMP did not demonstrate any correlation with TNFα-induced osteosarcoma cell invasion. Although NFκB is known to regulate TNFα-induced phenotypes, it may influence only motility and invasion, but not the MMP or laminin-mediated adhesion of these osteosarcoma cells.