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      Tobacco smoke induces production of chemokine CCL20 to promote lung cancer.

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          Abstract

          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.

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          Author and article information

          Journal
          Cancer Lett.
          Cancer letters
          1872-7980
          0304-3835
          Jul 10 2015
          : 363
          : 1
          Affiliations
          [1 ] State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences & Graduate School of the University of Chinese Academy of Sciences, Beijing 100101, China.
          [2 ] Department of Orthopedics, Provincial Hospital Affiliated to Shandong University, 324 Jing Wu Road, Jinan 250021, China.
          [3 ] Department of Central Laboratory, The First Hospital, Jilin University, Changchun 130032, China.
          [4 ] Department of Thoracic Surgery, China-Japan Friendship Hospital, Beijing 100029, China.
          [5 ] Department of Thoracic Surgery, The Cancer Hospital, Sun Yat-Sen University, Guangzhou 510060, China.
          [6 ] Department of Thoracic Surgery, Yunnan Cancer Hospital, Kunming 650106, China.
          [7 ] State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences & Graduate School of the University of Chinese Academy of Sciences, Beijing 100101, China. Electronic address: gbzhou@ioz.ac.cn.
          Article
          S0304-3835(15)00263-3
          10.1016/j.canlet.2015.04.005
          25864589
          cea5f8ee-96d1-41fa-9c66-324c61a18664
          Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.
          History

          CCL20,Lung cancer,NNK,Tobacco smoke
          CCL20, Lung cancer, NNK, Tobacco smoke

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