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 benzo(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, significantly attenuated BaP-induced lung cancer in mice, demonstrating CXCL13's critical role in PAH-induced lung carcinogenesis.
[1]Chinese Acad Sci, Inst Zool, State Key Lab Membrane Biol, Beijing, Peoples R China.
[2]Sun Yat Sen Univ, Ctr Canc, Dept Thorac Surg, Guangzhou 510275, Guangdong, Peoples R China.
[3]Kunming Med Univ, Affiliated Hosp 3, Dept Thorac Surg, Kunming, Peoples R China.
[4]First Peoples Hosp Qu Jing City, Dept Pathol, Qu Jing, Peoples R China.
[5]Chinese Peoples Liberat Army Gen Hosp, Dept Pathol, Beijing, Peoples R China.
[6]Chinese Acad Sci, Kunming Inst Zool, Lab Mol & Expt Pathol, Kunming, Peoples R China.
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