Nuclear Factor-κB (NF-κB) is important in tumor cell survival, apoptosis, angiogenic response, regulation of innate immunity and multiple other processes important for tumor progression. It is therefore centrally positioned to control the metastatic potential of cancer cells. As inflammation and cancer are clearly related, NF-κB may also mechanistically link host inflammatory response to tumor progression and metastasis. We have adopted an experimental metastasis model in which tumor cells (mammary or lung) are introduced via the tail vein of immunocompetent syngeneic mice resulting in metastatic lung tumors. In our model NF-κB activity can be monitored in both tumor cells and in the host using bioluminescent reporters. The Lewis lung cancer (LLC) and polyoma mammary tumor cells used in the study are stably transfected with an NF-κB-driven GFP-Luciferase reporter plasmid while NF-κB reporter mice (HLL) express luciferase under the control of a non-tissue specific NF-κB responsive promoter. NF-κB activity was modulated in the host lung using either intratracheal injection of recombinant adenoviral vectors or by using a novel doxycycline inducible transgenic model. Our results show that elevated NF-κB activity in the host increases metastatic potential of tumor cells. This suggests that a chronic inflammatory state in metastatic sites can accelerate tumor progression.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]