Minimal asbestos exposure in germline BAP1 heterozygous mice is associated with deregulated inflammatory response and increased risk of mesothelioma

dc.contributor.author Napolitano, Andrea
dc.contributor.author Pellegrini, Laura
dc.contributor.author Dey, A.
dc.contributor.author Larson, David
dc.contributor.author Tanji, Mika
dc.contributor.author Flores, Erin G.
dc.contributor.author Kendrick, Brian
dc.contributor.author Lapid, Danica
dc.contributor.author Powers, Amy
dc.contributor.author Kanodia, S.
dc.contributor.author Pastorino, Sandra
dc.contributor.author Pass, H.I.
dc.contributor.author Dixit, V.
dc.contributor.author Yang, Haining
dc.contributor.author Cabone, Michele
dc.date.accessioned 2016-03-10T03:04:36Z
dc.date.available 2016-03-10T03:04:36Z
dc.date.issued 2015-06
dc.description.abstract Germline BAP1 mutations predispose to several cancers, in particular malignant mesothelioma. Mesothelioma is an aggressive malignancy generally associated to professional exposure to asbestos. However, to date we found that none of the mesothelioma patients carrying germline BAP1 mutations were professionally exposed to asbestos. We hypothesized that germline BAP1 mutations might influence the asbestos-induced inflammatory response that is linked to asbestos carcinogenesis, thereby increasing the risk of developing mesothelioma after minimal exposure. Using a BAP1+/- mouse model, we found that, compared to their wild type littermates, BAP1+/- mice exposed to low-dose asbestos fibers showed significant alterations of the peritoneal inflammatory response, including significantly higher levels of pro-tumorigenic alternatively polarized M2 macrophages, and lower levels of several chemokines and cytokines. Consistent with these data, BAP1+/- mice had a significantly higher incidence of mesothelioma after exposure to very low doses of asbestos, doses that rarely induced mesothelioma in wild type mice. Our findings suggest that minimal exposure to carcinogenic fibers may significantly increase the risk of malignant mesothelioma in genetically predisposed individuals carrying germline BAP1 mutations, possibly via alterations of the inflammatory response. en_US
dc.format.extent 26 en_US
dc.identifier.doi 10.1038/onc.2015.243
dc.identifier.uri http://hdl.handle.net/10125/39964
dc.language.iso en-US en_US
dc.publisher Nature Oncogene en_US
dc.relation.uri http://www.nature.com/onc/journal/vaop/ncurrent/full/onc2015243a.html en_US
dc.subject BAP1 en_US
dc.subject BAP1 cancer syndrome en_US
dc.subject Germline en_US
dc.subject Mesothelioma en_US
dc.subject Asbestos en_US
dc.subject Dose en_US
dc.subject Inflammation en_US
dc.subject Macrophages en_US
dc.subject Polarization en_US
dc.subject M1 en_US
dc.subject M2 en_US
dc.title Minimal asbestos exposure in germline BAP1 heterozygous mice is associated with deregulated inflammatory response and increased risk of mesothelioma en_US
dc.type Article en_US
dc.type.dcmi Text en_US
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