Deciphering the Code between Air Pollution and Disease: The Effect of Particulate Matter on Cancer Hallmarks

Air pollution has been recognized as a global health problem, causing around 7 million deaths worldwide and representing one of the highest environmental crises that we are now facing. Close to 30% of new lung cancer cases are associated with air pollution, and the impact is more evident in major cities. In this review, we summarize and discuss the evidence regarding the effect of particulate matter (PM) and its impact in carcinogenesis, considering the “hallmarks of cancer” described by Hanahan and Weinberg in 2000 and 2011 as a guide to describing the findings that support the impact of particulate matter during the cancer continuum

The Road to Malignant Cell Transformation after Particulate Matter Exposure: From Oxidative Stress to Genotoxicity

In cells, oxidative stress is an imbalance between the production/accumulation of oxidants and the ability of the antioxidant system to detoxify these reactive products. Reactive oxygen species (ROS), cause multiple cellular damages through their interaction with biomolecules such as lipids, proteins, and DNA. Genotoxic damage caused by oxidative stress has become relevant since it can lead to mutation and play a central role in malignant transformation. The evidence describes chronic oxidative stress as an important factor implicated in all stages of the multistep carcinogenic process: initiation, promotion, and progression. In recent years, ambient air pollution by particulate matter (PM) has been cataloged as a cancer risk factor, increasing the incidence of different types of tumors. Epidemiological and toxicological evidence shows how PM-induced oxidative stress could mediate multiple events oriented to carcinogenesis, such as proliferative signaling, evasion of growth suppressors, resistance to cell death, induction of angiogenesis, and activation of invasion/metastasis pathways. In this review, we summarize the findings regarding the involvement of oxidative and genotoxic mechanisms generated by PM in malignant cell transformation. We also discuss the importance of new approaches oriented to studying the development of tumors associated with PM with more accuracy, pursuing the goal of weighing the impact of oxidative stress and genotoxicity as one of the main mechanisms associated with its carcinogenic potential

Particulate Matter (PM10) Promotes Cell Invasion through Epithelial–Mesenchymal Transition (EMT) by TGF-β Activation in A549 Lung Cells

Air pollution presents a major environmental problem, inducing harmful effects on human health. Particulate matter of 10 μm or less in diameter (PM10) is considered an important risk factor in lung carcinogenesis. Epithelial–mesenchymal transition (EMT) is a regulatory program capable of inducing invasion and metastasis in cancer. In this study, we demonstrated that PM10 treatment induced phosphorylation of SMAD2/3 and upregulation of SMAD4. We also reported that PM10 increased the expression and protein levels of TGFB1 (TGF-β), as well as EMT markers SNAI1 (Snail), SNAI2 (Slug), ZEB1 (ZEB1), CDH2 (N-cadherin), ACTA2 (α-SMA), and VIM (vimentin) in the lung A549 cell line. Cell exposed to PM10 also showed a decrease in the expression of CDH1 (E-cadherin). We also demonstrated that expression levels of these EMT markers were reduced when cells are transfected with small interfering RNAs (siRNAs) against TGFB1. Interestingly, phosphorylation of SMAD2/3 and upregulation of SMAD induced by PM10 were not affected by transfection of TGFB1 siRNAs. Finally, cells treated with PM10 exhibited an increase in the capacity of invasiveness because of EMT induction. Our results provide new evidence regarding the effect of PM10 in EMT and the acquisition of an invasive phenotype, a hallmark necessary for lung cancer progression