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

Aging (Albany NY). 2020 Jun 18;12(12):11579-11602. doi: 10.18632/aging.103319. Epub 2020 Jun 18.


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.

Keywords: EMT; IL-17a; NSCLC; PM2.5; metastasis.

MeSH terms

  • A549 Cells
  • Air Pollutants / adverse effects*
  • Animals
  • Beijing
  • Bronchoalveolar Lavage Fluid
  • Carcinoma, Non-Small-Cell Lung / etiology
  • Carcinoma, Non-Small-Cell Lung / secondary*
  • Environmental Monitoring / statistics & numerical data
  • Humans
  • Interleukin-17 / genetics
  • Interleukin-17 / metabolism*
  • Lung / pathology
  • Lung Neoplasms / etiology
  • Lung Neoplasms / pathology*
  • Male
  • Mice
  • Mice, Knockout
  • Particle Size
  • Particulate Matter / adverse effects*
  • Xenograft Model Antitumor Assays


  • Air Pollutants
  • IL17A protein, human
  • Il17a protein, mouse
  • Interleukin-17
  • Particulate Matter