More than 90% of lung cancers are caused by cigarette smoke and air pollution, with polycyclic aromatic hydrocarbons (PAHs) as key carcinogens. In Xuanwei City of Yunnan Province the lung cancer incidence is among the highest in China attributed to smoky coal combustion-generated PAH pollution. Here we screened for abnormal inflammatory factors in non-small cell lung cancers (NSCLCs) from Xuanwei and control regions (CR) where smoky coal was not used, and found that a chemokine CXCL13 was overexpressed in 63/70 (90%) of Xuanwei NSCLCs and 44/71 (62%) of smoker and 27/60 (45%) of non-smoker CR patients. CXCL13 overexpression was associated with the region Xuanwei and cigarette smoke. The key carcinogen bezo(a)pyrene (BaP) induced CXCL13 production in lung epithelial cells and in mice prior to development of detectable lung cancer. Deficiency in cxcl13 or its receptor, cxcr5, abrogated BaP-induced lung cancer in mice, demonstrating CXCL13's critical role in PAH-induced lung carcinogenesis.
Animal experimentation: Animal studies were conducted according to protocols approved by the Animal Ethics Committee of the Institute of Zoology, Chinese Academy of Sciences, with the approval ID of AEC2010070202.
Human subjects: The study was approved by the local research ethics committees of all participating sites; all lung cancer samples were collected with informed consent.
- David Barbie, Dana-Farber Cancer Institute, United States
© 2015, Wang et al.
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