title: Tobacco smoke induces production of chemokine CCL20 to promote lung cancer.
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.
authors: 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.
authors: Gui-Zhen
authors: GZ
authors: Wang
authors: 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.
authors: Xin
authors: X
authors: Cheng
authors: 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.
authors: Xin-Chun
authors: XC
authors: Li
authors: 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.
authors: Yong-Qiang
authors: YQ
authors: Liu
authors: Department of Orthopedics, Provincial Hospital Affiliated to Shandong University, 324 Jing Wu Road, Jinan 250021, China.
authors: Xian-Quan
authors: XQ
authors: Wang
authors: Department of Central Laboratory, The First Hospital, Jilin University, Changchun 130032, China.
authors: Xu
authors: X
authors: Shi
authors: Department of Thoracic Surgery, China-Japan Friendship Hospital, Beijing 100029, China.
authors: Zai-Yong
authors: ZY
authors: Wang
authors: Department of Thoracic Surgery, China-Japan Friendship Hospital, Beijing 100029, China.
authors: Yong-Qing
authors: YQ
authors: Guo
authors: Department of Thoracic Surgery, The Cancer Hospital, Sun Yat-Sen University, Guangzhou 510060, China.
authors: Zhe-Sheng
authors: ZS
authors: Wen
authors: Department of Thoracic Surgery, Yunnan Cancer Hospital, Kunming 650106, China.
authors: Yun-Chao
authors: YC
authors: Huang
authors: 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.
authors: Guang-Biao
authors: GB
authors: Zhou
mesh_terms: D000368:Aged; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D054418:Chemokine CCL20 / Q000235:genetics / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008175:Lung Neoplasms / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D034622:RNA Interference; D054399:Receptors, CCR6 / Q000378:metabolism; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects*; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation
chemical_list: D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; C108355:CCL20 protein, human; C106311:CCR6 protein, human; D054418:Chemokine CCL20; D018836:Inflammation Mediators; D054399:Receptors, CCR6; D012906:Smoke; D003907:Dexamethasone
keywords: CCL20; Lung cancer; NNK; Tobacco smoke