Functional roles of tumor necrosis factor‐related apoptosis‐inducing ligand– DR 5 interaction in B 16 F 10 cells by activating the nuclear factor‐κ B pathway to induce metastatic potential

Tumor necrosis factor‐related apoptosis‐inducing ligand ( TRAIL ) has been recognized as a promising target for cancer therapy because it can induce apoptotic cell death in tumor cells but not normal cells. Although TRAIL shows specific tumoricidal activity, resistance to TRAIL ‐induced apoptosis in some tumor cells has been considered a clinical obstacle of its application. It has been shown that TRAIL provides inflammatory signals that may contribute to the TRAIL ‐resistance of cancer cells; however, it is not known whether TRAIL itself is involved in malignant cancer cell behavior. In the present study, we examined the functional role of TRAIL in B 16 F 10 mouse melanoma cells, which are totally insensitive to TRAIL ‐induced apoptosis. By establishing B 16 F 10 cells stably expressing the nuclear factor‐κ B ( NF κ B )‐luciferase reporter gene, we found that TRAIL can activate NF κ B through its death receptor DR 5 in B 16 F 10 cells. Furthermore, TRAIL – DR 5 interaction not only promoted malignant behaviors of B 16 F 10 cells, such as cell proliferation and MMP ‐9 production, but also induced lung metastasis of B 16 F 10 cells in vivo . These findings may imply a contrary role for the TRAIL – DR 5 pathway in the inflammatory tumor microenvironment, in its ability to induce the metastatic potential of B 16 F 10 melanoma cells instead of inducing apoptosis.