Abstract
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.
Highlights
Air pollution is a diverse mixture of pollutants that originated from anthropogenic and natural sources, is comprised of particulate matter (PM), gases, organic compounds, metals, and others, such as microbes (Akimoto, 2003; Huang et al, 2014)
Using a microarray analysis of 84 cytokines/chemokines in tumor samples and their adjacent normal lung tissues of eight Highly polluted region (HPR) non-small cell lung cancers (NSCLCs), we found that the expression of four cytokines (IL-1F5, IL-1F9, MIF, and secreted phosphoprotein 1 (SPP1)) and seven chemokines (CXCL13, CCL7, CCL20, CCL26, CXCL6, CXCL9, and CXCL14) was increased in tumors compared with their counterpart normal lung tissues (Figure 1A)
ELISA showed that the CXCL13 serum concentration was higher in the HPR patients compared with the Control region (CR) patients, while the latter was higher than the healthy donors (Figure 1G)
Summary
Air pollution is a diverse mixture of pollutants that originated from anthropogenic and natural sources, is comprised of particulate matter (PM), gases (e.g., sulfur oxides, carbon monoxide, ozone), organic compounds (e.g., polycyclic aromatic hydrocarbons, PAHs), metals (e.g., lead, vanadium, and nickel), and others, such as microbes (Akimoto, 2003; Huang et al, 2014). Outdoor air pollution in cities and rural areas was estimated to cause 3.7 million premature deaths annually worldwide in 2012, including 220,000 deaths due to lung cancer (WHO, 2014). Outdoor (Loomis et al, 2013) and indoor (WHO, 2010) air pollution has been classified as a Group 1 carcinogen in humans by the International Agency for Research on Cancer (IARC) of WHO.
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