Atmospheric fine particulate matter and epithelial mesenchymal transition in pulmonary cells: state of the art and critical review of the in vitro studies

ABSTRACT

Exposure to fine particulate matter (PM_2.5) has been associated with several diseases including asthma, chronic obstructive pulmonary disease (COPD) and lung cancer. Mechanisms such as oxidative stress and inflammation are well-documented and are considered as the starting point of some of the pathological responses. However, a number of studies also focused on epithelial-mesenchymal transition (EMT), which is a biological process involved in fibrotic diseases and cancer progression notably via metastasis induction. Up until now, EMT was widely reported in vivo and in vitro in various cell types but investigations dealing with in vitro studies of PM_2.5 induced EMT in pulmonary cells are limited. Further, few investigations combined the necessary endpoints for validation of the EMT state in cells: such as expression of several surface, cytoskeleton or extracellular matrix biomarkers and activation of transcription markers and epigenetic factors. Studies explored various cell types, cultured under differing conditions and exposed for various durations to different doses. Such unharmonized protocols (1) might introduce bias, (2) make difficult comparison of results and (3) preclude reaching a definitive conclusion regarding the ability of airborne PM_2.5 to induce EMT in pulmonary cells. Some questions remain, in particular the specific PM_2.5 components responsible for EMT triggering. The aim of this review is to examine the available PM_2.5 induced EMT in vitro studies on pulmonary cells with special emphasis on the critical parameters considered to carry out future research in this field. This clarification appears necessary for production of reliable and comparable results.

KEYWORDS:

• Particulate matter
• PM_2.5
• epithelial-mesenchymal transition
• EMT
• pulmonary cells

Acknowledgments

Authors would like to thank the French Environment and Energy Management Agency (ADEME) (1962C0005) within the French National Research Program for Environmental and Occupational Health of ANSES for financial support. Margaux Cochard thanks the Hauts-de-France Region and ADEME for the financial support of her PhD. The “Unité de Chimie Environnementale et Interactions sur le Vivant” (UCEiV-UR4492) participates in the CLIMIBIO project, which is financially supported by the Hauts-de-France Region Council, the French Ministry of Higher Education and Research, and the European Regional Development Funds.