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 TNF alpha enhanced the invasiveness of two human osteosarcoma cell lines, OST and MNNG. TNF alpha treatment also induced tumor cell motility, adhesion to laminin, the expression of matrix metalloproteinase 9 (MMP9), and the nuclear translocation of nuclear factor kappaB (NF kappaB) in the osteosarcoma cells. Moreover, antioxidants inhibited TNF alpha -induced osteosarcoma cell invasion, motility and NF kappaB nuclear translocation, but not adhesion to laminin or MMP9 expression. NF kappaB decoy, another NF kappaB inhibitor, also inhibited TNF alpha -induced osteosarcoma cell invasion and motility. Therefore, motility and NF kappaB activation were possibly related to TNF alpha -induced osteosarcoma cell invasion. However, adhesion to laminin or MMP did not demonstrate any correlation with TNF alpha -induced osteosarcoma cell invasion. Although NF kappaB is known to regulate TNF alpha -induced phenotypes, it may influence only motility and invasion, but not the MMP or laminin-mediated adhesion of these osteosarcoma cells.