For the purpose of determining whether or not the activation of hepatic NF-κB is involved in the onset of metastatic tumors, a liver metastatic model induced in the spleen is used. When IKKβ is lacked in both hepatocytes and hematopoietically-derived cells, the onset of tumors is remarkably decreased. A tumor cell activates an adjacent bone marrow cell (Kupffer cell) to produce a mitogen such as interleukin (IL)-6, and the mitogen accelerates the proliferation of a tumor and neovascularization. The production of the mitogen depends on NF-κB in hematopoietically-derived Kupffer cells. In addition, the treatment with an anti-IL-6 receptor antibody can decrease the level of the onset of a metastatic tumor. Consequently, it is demonstrated that the metastasis of tumors depends on inflammations, and it is also demonstrated that the proinflammatory mediation which targets at Kupffer cells is useful in the chemoprevention of metastatic tumors. It is also demonstrated that the inhibition of an IKKβ/NF-κB signaling pathway, particularly IL-6, can be employed as an anti-metastasis agent.
