Inhibition of constitutive NF‐κB activity suppresses tumorigenicity of ewing sarcoma EW7 cells

Ewing sarcoma is 1 of the most aggressive tumors that can affect children and young adults. Despite advances in therapy, the prognosis remains poor emphasizing the need for defining new targets for treatment. We investigated a possible role of nuclear factor‐κB (NF‐κB) activity of Ewing sarcoma‐derived EW7 cells in their tumorigenicity. In these cells, expression of a degradation‐resistant form of the inhibitory factor IκBα inhibited NF‐κB activity without affecting their in vitro proliferation rate. It causes, however, a remarkable loss of their ability to generate tumors in nude mice that correlates with both a decrease in extracellular matrix (ECM) protein secretion and an acquisition of sensitivity to murine tumor necrosis factor α (TNFα)‐induced apoptosis. These data support the concept that NF‐κB activity plays a role in the tumorigenicity of Ewing sarcoma cells, identifying NF‐κB as a potential target for reducing Ewing tumor progression. © 2001 Wiley‐Liss, Inc.