Mouse cancer cells and bone-marrow macrophages expressing or silenced for IKKA and IKKB

In this study we used bioluminescent reporter mice to discover that transplantable tumors cause nuclear factor-kappa B activation in host macrophages. This effect is mostly aggravated in mouse models of malignant pleural effusion, is dependent on KRAS mutation status of tumor cells, and is delivered via secretory versican, a toll-like receptor 2 ligand. Versican, in turn activates nuclear factor-kappa B in host macrophages via the canonical inhibitor of nuclear factor-kappa B kinase beta (IKKbeta), resulting in release of myeloid-secreted interleukin-1beta in the tumor microenvironment. Silencing of versican in cancer cells or conditional deletion of IKKbeta in macrophages abrogates myeloid nuclear factor-kappa B activation as well as tumor progression. Compare differential gene expression between mouse cancer cells and bone-marrow macrophages expressing or silenced for IKKA and IKKB