Long-term PM(2.5) exposure increases the risk of non-small cell lung cancer (NSCLC) progression by enhancing interleukin-17a (IL-17a)-regulated proliferation and metastasis

PM(2.5) is a class of airborne particles and droplets with sustained high levels in many developing countries. Epidemiological studies have indicated that PM(2.5) is closely associated with the increased morbidity and mortality of lung cancer in the world. Unfortunately, the effects of PM(2.5) on lung cancer are largely unknown. In the present study, we attempted to explore the role of PM(2.5) in the etiology of NSCLC. Here, we found that long-term PM(2.5) exposure led to significant pulmonary injury. Epithelial-mesenchymal transition (EMT) and cancer stem cells (CSC) properties were highly induced by PM(2.5) exposure. EMT was evidenced by the significant up-regulation of MMP2, MMP9, TGF-β1, α-SMA, Fibronectin and Vimentin. Lung cancer progression was associated with the increased expression of Kras, c-Myc, breast cancer resistance protein BCRP (ABCG2), OCT4, SOX2 and Aldh1a1, but the decreased expression of p53 and PTEN. Importantly, mice with IL-17a knockout (IL-17a(-/-)) showed significantly alleviated lung injury and CSC properties following PM(2.5) exposure. Also, IL-17a(-/-)-attenuated tumor growth was recovered in PM(2.5)-exposed mice injected with recombinant mouse IL-17a, accompanied with significantly restored lung metastasis. Taken together, these data revealed that PM(2.5) could promote the progression of lung cancer by enhancing the proliferation and metastasis through IL-17a signaling.