An Essential Role for Interleukin 6 in Lung Carcinogenesis
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Abstract
Lung cancer is the leading cause of cancer related deaths worldwide. Epidemiological studies have shown that patients with chronic obstructive pulmonary disease (COPD) have a higher risk of developing lung cancer, when compared to smokers without COPD. Moreover, we showed that a bacterial lysate-induced COPD-like airway inflammation promotes lung carcinogenesis in a K-ras mutant (CC-LR) mouse model. In our CC-LR mouse model, particularly high levels of interleukin 6 (IL-6) were observed. IL-6 is up-regulated in many types of inflammatory diseases and cancers, such as non-small cell lung cancer. Therefore, we genetically ablated IL-6 in the CC-LR mice, and found an essential role for IL-6 in cancer promotion in this K-ras induced model of lung cancer. In this study, we focused on blocking the IL-6 pathway using a monoclonal anti-IL-6 antibody therapy. CC-LR mice were injected intraperitoneally with a 20 mg/kg dose of monoclonal anti-IL-6 rat IgG1, twice a week, for a period of eight weeks. Anti-IL-6 treated mice were also exposed to the aerosolized bacterial lysate, weekly for a period of 8 weeks. Treatment with anti IL-6 antibody did not change the quantity of inflammatory cells in bronchoalveolar lavage fluid (BALF) of CC-LR mice. However, it not only inhibited intrinsic lung cancer development by ~78% (4.6-fold) in the absence of COPD-like inflammation, but also inhibited the tumor promoting effect of extrinsic NTHi-induced COPD-like airway inflammation by ~74% (3.9-fold). Here we propose a new therapeutic strategy for treatment of lung cancer patients with K-ras mutations, and possible preventive strategy in patients with COPD, using anti-IL-6 therapy.
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This presentation is supported by the National Cancer Institute through the U54 CA096297/CA096300: UPR/MDACC Partnership for Excellence in Cancer Research Training Program.