Colon cancer-derived factors activate NF-κB in myeloid cells via TLR2 to link inflammation and tumorigenesis

Abstract

The exact mechanism for the contribution of NF-κB activation during colon carcinogenesis is unclear. The present study aimed to determine the manner in which colon cancer cells induce inflammatory responses in order to link tumor growth. Macrophages were stimulated with cultured medium from the supernatants of several colon cancer cell lines. Macrophage accumulation and NF-κB activation were observed in samples that were stimulated with supernatant from tumor cells that showed constitutive NF-κB activity. NF-κB activation in the stimulated macrophages was dependent on TLR2 and IKKβ, but not TLR4. Various cytokines, such as IL-6, were induced in a TLR2-dependent manner. Tumor cells that were cultured with the supernatant of macrophages originally stimulated with the tumor cell cultured media grew more rapidly than those stimulated with the supernatant of unstimulated macrophages. Taken together, colon cancer-derived factors induce the accumulation of macrophages and activate NF-κB through a TLR2-dependent mechanism, suggesting an important link between inflammation and tumor growth.