Function of myeloid NFkB in cigarette smoke induced lung carcinoma proliferation

Objective: From clinical investigation it is known that the presence of COPD significantly increases the risk of developing lung cancer. COPD-specific inflammation likely increases the speed of tumor growth. To investigate the function of myeloid NFκB in cigarette smoke (CS) induced lung tumor proliferation.

Methods: 5×10⁵ Lewis lung carcinoma (LLC) cells were intravenously injected into wild type and myeloid p65 deficient (p65^–/–) C57/BL6 mice. After 7 days, the mice were smoked for 7 days using the TE-10 smoking machine (3h, 300±15mg/m³ particles). Control groups were incubated with filtered air. At day 21, the lungs were removed and histologically examined. Tumor proliferation was determined with the help of western-blot, immunohistochemistry, qRT-PCR, and ELISA.

Results: In CS exposed wild type mice, the number of tumor nodules were significantly higher compared to air exposed control animals. However, in CS exposed p65^–/– mice, the tumor growth was significantly lower compared to wild type mice. CS exposure resulted in enhanced expression of the proliferation markers PCNA and CyclinD1 in lung tumors of wild type animals shown by qRT-PCR and immunohistochemistry. This was not observed in p65^–/– mice. In contrast to p65 ^–/– mice, CS exposure of wild type mice resulted in the secretion of IL-6, KC, MMP9, and TNFα as well as in the activation of STAT3 and C-jun signalling in tumor cells.

Conclusion: These results show that CS promotes the growth of cancer cells and that myeloid NFκB plays an important role in this process. Functional myeloid NFκB is required for the activation of markers of inflammation and proliferation as well as of signalling pathway known to be involved in the formation and growth of tumors.