Air pollution and Lung Cancer
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Curr Environ Health Rep. 2023 Dec 6;10(4):478–489. doi: 10.1007/s40572-023-00421-8
Air Pollution and Lung Cancer: Contributions of
Extracellular Vesicles as Pathogenic Mechanisms and Clinical Utility
Jonathan González-Ruíz 1, Andrea ABaccarelli 2, David Cantu-de-Leon 1, Diddier Prada3
Introduction
In recent years, the adverse effects of air pollution on human health have become a growing concern worldwide [1, 2].
The quality of the air we breathe plays a crucial role in maintaining our well-being, particularly when it comes to lung health [3].
Prolonged exposure to air pollutants may induce a wide range of respiratory symptoms, including coughing, wheezing, shortness of breath, and chest tightness, all of them linked with acute and long-term effects [4].
Air pollutants, consisting of a complex mixture of harmful particles and gases, have been linked to a wide range of respiratory disorders, including asthma, chronic obstructive pulmonary disease (COPD), reduced lung function, and lung cancer,
in particular, non-small cell lung cancer (NSCLC) [5]. The association between environmental air pollutants and lung cancer has been extensively studied [3].
In October 2013, the specialized cancer agency of the World Health Organization, the International Agency for Research on Cancer (IARC) announced that outdoor air pollution was classified as carcinogenic to humans (Group 1) [6].
Further epidemiological studies have consistently demonstrated a strong link between prolonged exposure to air pollutants and the development of lung cancer [7].
Lung cancer ranks as the most prevalent cancer and remains the primary cause of cancer-related deaths and is a significant global health issue,
with current worldwide statistics reflecting its magnitude. Across the globe, lung cancer stands as the most common cancer, and its impact is substantial.
In 2022, there were over 2 million new cases of lung cancer reported, accounting for approximately 11% of all new cancer diagnoses [8].
Unfortunately, lung cancer continues to be the leading cause of cancer-related deaths globally. While this cancer affects both men and women, the statistics reveal significant sex disparities.
Among men, lung cancer remains the leading cause of cancer-related mortality.
Among women, it ranks second only to breast cancer, being a major cause of mortality among them.
These statistics underscore the importance of understanding both the overall prevalence of lung cancer and the gender-specific differences in its incidence and consequences [9].
It is also the third most common cancer, following breast and colorectal cancers, and the second leading cause of cancer death after breast cancer among women vulnerable groups around the world include individuals with limited access to healthcare, low socioeconomic status, heavy tobacco user, and those living in highly polluted areas [10].
Air pollution may activate several cellular, molecular, and systemic changes, including inflammation, oxidative damage, microthrombosis, epigenomic changes, and activation of several other cellular responses, including the release of extracellular vesicles (EVs) [11••].
EVs encompass a heterogeneous group of vesicles that can be classified into three main subtypes, microvesicles, exosomes, and apoptotic bodies [12].
EVs are membrane-bound structures that are shed from the plasma membrane of cells [13]. They encapsulate a diverse range of molecules, including peptides, nucleic acids (such as microRNAs, mRNAs, and long noncoding RNAs), lipids, and metabolites. This cargo can be transferred to recipient cells, modulating their function and behavior [14].
In normal cells, EVs play an important role in intercellular communication by allowing cells to exchange information and signals with each other [15]. EVs have been shown to be involved in a variety of physiological and pathological processes, including immune regulation, tissue repair and regeneration, inflammation, and angiogenesis [16]. EVs can be released practically by any cell, including cancer cells [17], and have been implicated in tumor growth, metastasis, and drug resistance [18]. This review examines the mechanisms of air pollution’s impact on lung cancer development, with a focus on the contribution of extracellular vesicles to carcinogenesis and cancer progression. Additionally, it explores the potential utility of these vesicles in clinical settings for lung cancer (i.e., NSCLC).
Air Pollution and Its Impact on Human Health
Air pollution components contain particulate matter (PM) and gases, including volatile organic compounds.
Particulate matter is a common component of air pollution and consists of tiny particles suspended in the air [19].
These particles can be classified based on their size, with particles with a diameter of 2.5 µm or less (PM2.5) and PM10 (10 µm or less), also called coarse particles, and ultrafine particles (PM0.1), all of them being studied in
relation to lung cancer [20].
PM2.5 can penetrate deep into the respiratory system, reaching the lungs’ alveolar regions [21].
Inhaled fine PM deposited on the surface of the airways may either stay intact or partially dissolve but can also be cleared by mucociliary clearance and phagocytosis [22]
. PM can carry various carcinogens, such as polycyclic aromatic hydrocarbons (PAHs), heavy metals, and organic compounds, which have been linked to cancer development, including in the lungs [23].
Air pollution gases include nitrogen oxides (NOx: NO and NO2) and sulfur dioxide (SO2), which are produced primarily from combustion processes, such as those occurring in vehicle engines, power plants, and industrial facilities [24]. These pollutants can react with other compounds in the atmosphere to form secondary pollutants, such as nitric acid (HNO3) and ozone (O3) [25].
Studies have shown that exposure to nitrogen oxides, particularly in combination with other pollutants, increases the risk of lung cancer [26].
O3, a key component of photochemical smog, is another important air pollutant formed by the reaction of nitrogen oxides with volatile organic compounds (VOCs) in the presence of sunlight [27].
Prolonged exposure to ozone has been associated with adverse respiratory effects, and recent research also indicates a potential link between ozone exposure and lung cancer development [28].
Volatile organic compounds are also present in air pollution and are emitted from a wide range of sources, including industrial processes, vehicle emissions, and solvents [29].
Some VOCs, such as benzene, formaldehyde, and 1,3-butadiene, have been classified as carcinogens by the IARC [30].
All these pollutants may act in cells and tissues individually but also as mixtures. Therefore, air pollution includes a variety of compounds that, after long-term exposure, can contribute to an increased risk of developing lung cancer, particularly non-small cell lung cancer (NSCLC) [31].
Air Pollution and the Development of Lung Cancer: Potential Mechanisms of Damage and Relevance of EVs
Several mechanisms that could lead to lung carcinogenesis are activated by air pollutants, individually and as mixtures.
The most studied factors contributing to lung carcinogenesis include low-grade, chronic inflammation, oxidative stress, direct mutagenesis, epigenetic changes, and mitochondrial and endothelial dysfunction, but there are many others. EVs can contribute to some of these mechanisms to carry on signals to other cells and even contribute to adapting to air pollution damage. A summary of air pollution-related damage and the role
of EVs is shown in Fig. 1.
Fig. 1.
Conclusions
Addressing the impact of ambient air pollutants on lung health is highly relevant due to the adverse effects these pollutants have on respiratory symptoms,
lung function, and the development of lung cancer [121••]. This risk is more prominent in a climate change context with an increased number of wildfires worldwide [122].
The link between air pollutants and lung cancer is now well-established, with particulate matter, NOx, PM2.5, and volatile organic compounds being key contributors [26, 121••].
These pollutants can carry direct carcinogens and induce systemic, long-term inflammation, and oxidative stress in the lung cells, leading to DNA damage, mutations, epigenetic changes, the release of EVs, and the promotion of tumor growth and progression [59, 123]. Inflammatory signaling pathways, sometimes modulated by EVs, facilitate a tumor-promoting microenvironment that supports the development of lung cancer [124•].
Effective strategies and interventions to mitigate the harmful effects of air pollutants, including developing biomonitoring of these interventions, which could include EV and EV-cargo, on lung health are needed [125•]
. By addressing air pollution exposures in multiple ways (e.g., promoting clean energy sources, improving industrial practices with stricter emission standards, mandating and incentivizing stricter fuel efficiency standards for vehicles, strengthening air quality standards and regulations, reduce deforestation),
we can protect public health and improve outcomes for individuals affected by air pollution-related lung cancer [121••, 126].
EVs are critical components of liquid biopsy that will revolutionize medical follow-up in clinical oncology, especially in lung cancer, analyzing not only their number but their composition (miRNAs, lncRNAs, metabolites, peptides) and understanding tumor phenotypes in plasma without needing access to the tumors directly [127].
Very nice article!!!
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