Tobacco smoke induces production of chemokine CCL20 to promote lung cancer

• Published in: Cancer letters Vol. 363; no. 1; pp. 60 - 70
• Main Authors: Wang, Gui-Zhen, Cheng, Xin, Li, Xin-Chun, Liu, Yong-Qiang, Wang, Xian-Quan, Shi, Xu, Wang, Zai-Yong, Guo, Yong-Qing, Wen, Zhe-Sheng, Huang, Yun-Chao, Zhou, Guang-Biao
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 10.07.2015; Elsevier Limited
• Subjects: Aged; Animals; Anti-Inflammatory Agents - pharmacology; Antineoplastic Agents - pharmacology; Case-Control Studies; CCL20; Cell growth; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - metabolism; Cell Transformation, Neoplastic - pathology; Chemokine CCL20 - genetics; Chemokine CCL20 - metabolism; Chemokines; Dexamethasone - pharmacology; Female; Gene Expression Regulation, Neoplastic; Hematology, Oncology and Palliative Medicine; Humans; Inflammation Mediators - metabolism; Laboratory animals; Lung - drug effects; Lung - metabolism; Lung - pathology; Lung cancer; Lung Neoplasms - etiology; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Male; Medical prognosis; Mice; Middle Aged; Mutation; Neoplasm Invasiveness; NNK; Patients; Polycyclic aromatic hydrocarbons; Prognosis; Receptors, CCR6 - metabolism; RNA Interference; Rodents; Smoke - adverse effects; Smoking - adverse effects; Time Factors; Tobacco smoke; Transfection; Tumorigenesis; Up-Regulation; Tobacco smoke; NNK; CCL20; Lung cancer
• ISSN: 0304-3835; 1872-7980; 1872-7980
• DOI: 10.1016/j.canlet.2015.04.005

•Chemokine CCL20 was overexpressed in smoker lung cancers.•The expression of CCL20 was inversely associated with prognosis.•Tobacco carcinogen NNK induced the production of CCL20.•CCL20 promoted lung cancer cell proliferation and migration. Tobacco kills nearly 6 million people each year, and 90% of the annual 1.59 million lung cancer deaths worldwide are caused by cigarette smoke. Clinically, a long latency is required for individuals to develop lung cancer since they were first exposed to smoking. In this study, we aimed to identify clinical relevant inflammatory factors that are critical for carcinogenesis by treating normal human lung epithelial cells with tobacco carcinogen nicotine-derived nitrosaminoketone (NNK) for a long period (60 days) and systematic screening in 84 cytokines/chemokines. We found that a chemokine CCL20 was significantly up-regulated by NNK, and in 78/173 (45.1%) patients the expression of CCL20 was higher in tumor samples than their adjacent normal lung tissues. Interestingly, CCL20 was up-regulated in 48/92 (52.2%) smoker and 29/78 (37.2%) nonsmoker patients (p = 0.05), and high CCL20 was associated with poor prognosis. NNK induced the production of CCL20, which promoted lung cancer cell proliferation and migration. In addition, an anti-inflammation drug, dexamethasone, inhibited NNK-induced CCL20 production and suppressed lung cancer in vitro and in vivo. These results indicate that CCL20 is crucial for tobacco smoke-caused lung cancer, and anti-CCL20 could be a rational approach to fight against this deadly disease.