Tobacco smoke induces production of chemokine CCL20 to promote lung cancer
Tobacco smoke induces production of chemokine CCL20 to promote lung cancer
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DOI：
10.1016/j.canlet.2015.04.005
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发表时间：
2015-07-10
期刊：
影响因子：
9.7
通讯作者：
Zhou, Guang-Biao
中科院分区：
文献类型：
--
作者：
Wang, Gui-Zhen;Cheng, Xin;Zhou, Guang-Biao
烟草每年导致近600万人死亡，全球每年159万肺癌死亡人数中有90%是由吸烟引起的。临床上，个体自首次暴露于吸烟后，需要较长的潜伏期才能患上肺癌。在这项研究中，我们的目的是确定临床相关的炎症因子是至关重要的致癌作用，通过治疗正常人肺上皮细胞与烟草致癌物尼古丁衍生的亚硝胺酮（NNK）的一个较长的时间（60天）和系统的筛选84细胞因子/趋化因子。我们发现趋化因子CCL 20被NNK显著上调，并且在78/173（45.1%）的患者中，CCL 20在肿瘤样品中的表达高于其邻近的正常肺组织。有趣的是，在48/92（52.2%）吸烟者和29/78（37.2%）非吸烟者患者中，CCL 20上调（p = 0.05），高CCL 20与不良预后相关。NNK诱导产生CCL 20，其促进肺癌细胞增殖和迁移。此外，一种抗炎药物地塞米松在体外和体内抑制NNK诱导的CCL 20产生并抑制肺癌。这些结果表明，CCL 20对烟草烟雾引起的肺癌至关重要，抗CCL 20可能是对抗这种致命疾病的合理方法。(C)2015年，作者。出版社：Elsevier爱尔兰Ltd.
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. (C) 2015 The Authors. Published by Elsevier Ireland Ltd.