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.

Xie Chao,Han Yun Wei,Dong Wei,Li Lan Lan,Liu Yi

doi:10.18632/aging.103319

Abstract

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.

Highlights

Particulate matter (PM) is a class of air pollutants, and consists of airborne solid particles and liquid droplets [1]
These results showed that long-term PM2.5 exposure led to severe pulmonary injury in mice
NSCLC cells cultured in the conditional medium from PM2.5-incubated Th17 cells exhibited markedly increased cell proliferation and Epithelial-mesenchymal transition (EMT) processes

Summary

Introduction

Particulate matter (PM) is a class of air pollutants, and consists of airborne solid particles and liquid droplets [1]. Epidemiological studies have indicated that the increasingly serious air pollution and PM2.5 levels are closely associated with health-related issues, including the enhanced hospitalization, increased mortality and mortality because of respiratory problems, shortened lifespan due to longterm PM2.5 exposure, as well as the up-regulated incidence and severity of lung cancer [4,5,6]. Some potential molecular mechanisms have been involved in the progression of lung injury triggered by PM2.5 exposure, including excessive oxidative stress, proinflammatory response and apoptotic cell death [7,8,9]. It is necessary to thoroughly investigate the mechanisms in NSCLC after exposure to particulate matter to better characterize gene-environment interactions and epigenetic influences on cancer exacerbation

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