Research Paper Volume 12, Issue 12 pp 11579—11602
Long-term PM2.5 exposure increases the risk of non-small cell lung cancer (NSCLC) progression by enhancing interleukin-17a (IL-17a)-regulated proliferation and metastasis
- 1 Department of Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, Shandong Province, P.R. China
- 2 Centers of Disease Control and Prevention of Shandong Province, Jinan 250014, Shandong Province, P.R. China
- 3 Affiliated Hospital of Binzhou Medical College, Binzhou 256603, Shandong Province, P.R. China
- 4 Department of Oncology, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Shihuan Province, P.R. China
Received: February 11, 2020 Accepted: April 28, 2020 Published: June 18, 2020https://doi.org/10.18632/aging.103319
How to Cite
Copyright © 2020 Chao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PM2.5 is a class of airborne particles and droplets with sustained high levels in many developing countries. Epidemiological studies have indicated that PM2.5 is closely associated with the increased morbidity and mortality of lung cancer in the world. Unfortunately, the effects of PM2.5 on lung cancer are largely unknown. In the present study, we attempted to explore the role of PM2.5 in the etiology of NSCLC. Here, we found that long-term PM2.5 exposure led to significant pulmonary injury. Epithelial-mesenchymal transition (EMT) and cancer stem cells (CSC) properties were highly induced by PM2.5 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 PM2.5 exposure. Also, IL-17a-/--attenuated tumor growth was recovered in PM2.5-exposed mice injected with recombinant mouse IL-17a, accompanied with significantly restored lung metastasis. Taken together, these data revealed that PM2.5 could promote the progression of lung cancer by enhancing the proliferation and metastasis through IL-17a signaling.