How asbestos and other fibers cause mesothelioma

Abstract

Mesothelioma has long been associated with the exposure to asbestos, which was largely used in manufacturing activities. Toxicology studies in vitro and in vivo demonstrated that asbestos fibers were carcinogenic, and epidemiology studies revealed that asbestos exposure was paralleled by the increase in the incidence of mesothelioma and related mortality rates. More recently, the role of chronic inflammation and the molecular mechanisms involved in carcinogenesis by mineral fibers were elucidated following the discovery of the roles of HMGB1 and inflammasome. A change of paradigm was the discovery of a prevalence of mesotheliomas attributable to inherited mutations of cancer susceptibility genes. The discovery of BAP1 as a predisposition gene for the development of familial mesothelioma and other cancers implemented genome studies in patients with mesothelioma and routine clinical surveys in individuals at risk to identify germline mutations associated with cancers included in the BAP1 syndrome. A further progress in the approach to asbestos-related malignancy was the adoption of combined genetics and environmental analyses according to the model of gene-environment (GxE) interactions. This review aims at updating on the most recently discovered mechanisms of tumorigenesis and the pivotal role of GxE interactions.

Inorganic Fiber Lung Burden in Subjects with Occupational and/or Anthropogenic Environmental Asbestos Exposure in Broni (Pavia, Northern Italy): An SEM-EDS Study on Autoptic Samples

“…In subjects who died with asbestosis, compared to MM patients, a higher concentration of ABs was observed. Even though this can be related simply to the higher concentration of asbestos fibers in those subjects, resulting in AB formation (consistent with the significant correlation between asbestos fibers and ABs), this finding suggests the hypothesis that the formation of ABs, one of the most controversial and unclear points in the cellular reaction to asbestos, might be the expression of a different biological response to asbestos, leading to a stronger capability to try to isolate and neutralize asbestos [ 1 , 41 , 42 ]. In other words, this finding may reflect a protective role of the fiber coating in the lung microenvironment.…”

“…The word asbestos defines mineral species that occur as bundles of fibers and that can be separated into thin threads. They are classified as asbestos by World Health Organization (WHO) when they occur in a respirable size with certain dimensions (length > 5 µm, width < 3 µm, aspect ratio greater than or equal to 3:1 [ 1 ]). Six different minerals belong to the asbestos group: actinolite asbestos, tremolite asbestos, anthophyllite asbestos, grunerite asbestos (also called amosite from its commercial name, which is an acronym for Asbestos Mines of South Africa), crocidolite, and chrysotile (the first five are amphiboles, whereas chrysotile is a serpentine), according to the international nomenclature.…”

The Dark Side of the Force: When the Immune System Is the Fuel of Tumor Onset

“…The inhalation of asbestos fibers in the lungs stimulates long-lasting reactive inflammation in macrophages and in mesothelial cells, which is non-resolving, due to the non-degradable properties of these fibers [92,93]. Over several years, this unleashed inflammation causes DNA damage, accumulation of DNA mutations and, ultimately, neoplastic transformation [94]. further demonstrated that the increase in these interleukins w blocked using the IL-1R antagonist Anakinra, both in vitro and in vivo [104].…”

Critical Roles of Tumor Extracellular Vesicles in the Microenvironment of Thoracic Cancers

“…Lung cancers can be divided into two major subtypes based on their cell morphologies: small-cell lung cancer (SCLC) (~15%) and non-small cell lung cancer (NSCLC) (~85%), which includes squamous cell carcinoma, adenocarcinoma, and large cell carcinoma [ 1 ]. Long-term smoking is one of its leading causes, whereas exposure to asbestos fibers has been associated with MPM for a long time now [ 2 , 3 ]. MPM is a cancer formed mainly in the pleura, a membrane covering lungs and the inner side of the ribs.…”