Malignant pleural mesothelioma: history, controversy and future of a manmade epidemic

Abstract

Asbestos is the term for a family of naturally occurring minerals that have been used on a small scale since ancient times. Industrialisation demanded increased mining and refining in the 20th century, and in 1960, Wagner, Sleggs and Marchand from South Africa linked asbestos to mesothelioma, paving the way to the current knowledge of the aetiology, epidemiology and biology of malignant pleural mesothelioma. Pleural mesothelioma is one of the most lethal cancers, with increasing incidence worldwide. This review will give some snapshots of the history of pleural mesothelioma discovery, and the body of epidemiological and biological research, including some of the controversies and unresolved questions. Translational research is currently unravelling novel circulating biomarkers for earlier diagnosis and novel treatment targets. Current breakthrough discoveries of clinically promising noninvasive biomarkers, such as the 13-protein signature, microRNAs and the BAP1 mesothelioma/cancer syndrome, are highlighted. The asbestos history is a lesson to not be repeated, but here we also review recent in vivo and in vitro studies showing that manmade carbon nanofibres could pose a similar danger to human health. This should be taken seriously by regulatory bodies to ensure thorough testing of novel materials before release in the society.

FIGURE 1

Bucket shape pottery from Telemark, also found in several other areas in Norway, from the Bronze Age to the Roman period (400–575 AD). They were used for cooking and storage of food, with estimated asbestos content of 65–80%. Image courtesy of Asbjørn Engevik, University Museum of Bergen, University of Bergen, Bergen, Norway. © Svein Skaare, University Museum of Bergen.

FIGURE 2

Cumulative amounts in 5-year periods from 1946 to 2010 of import of raw asbestos to Norway (data from Statistics Norway (www.ssb.no), 2002), incidence rates of malignant mesothelioma per 100 000 among males and females in Norway (International Classification of Diseases (10th Edition) diagnosis code C45; data from the Norwegian Cancer Registry (www.kreftregisteret.no)) and cumulative number of publications in PubMed with the key word “mesothelioma”.

FIGURE 3

Representation of the normal parietal pleura, the visceral pleura and pleural mesothelioma with the most abundant cell types. Reproduced from [50] with permission from the publisher.

FIGURE 4

Differential gene expression in human samples of the parietal pleura (PP), the visceral pleura (VP) and mesothelioma (meso). PP and PV from the same noncancer patients were analysed with a genome-wide mRNA array (unpublished observations). Tight junctions are much more abundant in the visceral pleura, and several claudins, including the claudin 18 gene (CLDN18), were highly expressed in VP. The type 2 neurotrophic tyrosine kinase receptor gene (NTRK2), which is abundantly expressed in nerve cells, is highly expressed in the PP. Both CLDN18 and NTRK2 had low expression in most of the mesotheliomas analysed. OD: optical density.

FIGURE 5

Pleural hazard of exposure to carbon nanotubes (CNTs). a) Structures of single-walled CNTs (SWCNTs) and multi-walled CNTs (MWCNTs) derived from buckminsterfullerene (C₆₀). The structure of a SWCNT (<0.4 nm in diameter) can be conceptualised by wrapping a one-atom-thick layer of graphite (or graphene) into a seamless cylinder. MWCNTs consist of multiple layers of graphite rolled on themselves to form a tube shape with an interlayer spacing of 3.4 Å and a diameter ranging from 1 to 50 nm. b) Schematic sequence of steps leading to pleural damage and/or malignant transformation as a consequence of exposure to biopersistent fibres. Long fibres and CNTs are retained at stomatal openings and induce an inflammatory oxidative stress response, which leads to aberrant reactions at the parietal pleura. Accordingly, the primary lesion caused by biopersistent fibres might form at the parietal pleural; this fact is reflected in pleural mesothelioma staging, where the early mesothelioma is confined to the parietal pleura while more advanced mesothelioma involves the visceral layer. LC: lymph channel; F: fibre; VP: visceral pleura; PP: parietal pleura; PS: pleural space; S: space c) Increasing literature on lung and pleura toxicity induced by CNTs in PubMed, searching for “CNT and pleural toxicity + CNT and mesothelioma”.