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Minimal asbestos exposure in germline BAP1 heterozygous mice is associated with deregulated inflammatory response and increased risk of mesothelioma
|Title:||Minimal asbestos exposure in germline BAP1 heterozygous mice is associated with deregulated inflammatory response and increased risk of mesothelioma|
show 10 moreFlores, Erin G.
BAP1 cancer syndrome
show 6 moreDose
|Issue Date:||Jun 2015|
|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.
|Appears in Collections:||University of Hawaii Cancer Center / Cancer Research Center Faculty & Researcher Works|
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