Asbestos accelerates disease onset in a genetic model of malignant pleural mesothelioma

Farahmand, P. et al. (2023) Asbestos accelerates disease onset in a genetic model of malignant pleural mesothelioma. Frontiers in Toxicology, 5, 1200650. (doi: 10.3389/ftox.2023.1200650) (PMID:37441092) (PMCID:PMC10333928)

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Abstract

Hypothesis: Asbestos-driven inflammation contributes to malignant pleural mesothelioma beyond the acquisition of rate-limiting mutations. Methods: Genetically modified conditional allelic mice that were previously shown to develop mesothelioma in the absence of exposure to asbestos were induced with lentiviral vector expressing Cre recombinase with and without intrapleural injection of amosite asbestos and monitored until symptoms required euthanasia. Resulting tumours were examined histologically and by immunohistochemistry for expression of lineage markers and immune cell infiltration. Results: Injection of asbestos dramatically accelerated disease onset and end-stage tumour burden. Tumours developed in the presence of asbestos showed increased macrophage infiltration. Pharmacological suppression of macrophages in mice with established tumours failed to extend survival or to enhance response to chemotherapy. Conclusion: Asbestos-driven inflammation contributes to the severity of mesothelioma beyond the acquisition of rate-limiting mutations, however, targeted suppression of macrophages in established epithelioid mesothelioma showed no therapeutic benefit.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Monteverde, Tiziana and Gyuraszova, Dr Katarina and Murphy, Professor Daniel and Farahmand, Dr Pooyeh and Lewis, Dr David and ROONEY, Dr CLAIRE and Jayasekera, Dr Geeshath and Le Quesne, Professor John and Blyth, Professor Kevin and Johnson, Ms Emma and Malviya, Dr Gaurav and Carlin, Dr Leo
Authors: Farahmand, P., Gyuraszova, K., Rooney, C., Raffo-Iraolagoitia, X. L., Jayasekera, G., Hedley, A., Johnson, E., Chernova, T., Malviya, G., Hall, H., Monteverde, T., Blyth, K., Duffin, R., Carlin, L. M., Lewis, D., le Quesne, J., MacFarlane, M., and Murphy, D. J.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Frontiers in Toxicology
Publisher:Frontiers Media
ISSN:2673-3080
ISSN (Online):2673-3080
Copyright Holders:Copyright © 2023 Farahmand, Gyuraszova, Rooney, Raffo-Iraolagoitia, Jayasekera, Hedley, Johnson, Chernova, Malviya, Hall, Monteverde, Blyth, Duffin, Carlin, Lewis, Le Quesne, MacFarlane and Murphy
First Published:First published in Frontiers in Toxicology 5:1200650
Publisher Policy:Reproduced under a Creative Commons licence

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
309830Manipulating the immune microenvironment in Malignant Pleural Mesothelioma (MPM)Claire RooneyOffice of the Chief Scientific Adviser (CSO)PCL/18/06CS - Beatson Institute for Cancer Research
168492A versatile spatio-temporally inducible genetically engineered mouse model of mesotheliomaDaniel MurphyBritish Lung Foundation (BLF)APHD13-5CS - Beatson Institute for Cancer Research
300925Meso-ORIGINS Feasibility StudyKevin BlythJune Hancock Mesothelioma Research Fund (JHANMESO)JH/17/03Institute of Infection, Immunity & Inflammation
303957Pre-clinical in vivo evaluation of immuno-modulatory therapy in MPMDaniel MurphyBritish Lung Foundation (BLF)MKMRFPG18-4CS - Beatson Institute for Cancer Research
Medical Research Council (MRC)MC_UU_000222/5
306544PREDICT-Meso: PRE-malignant Drivers Combined with Target-Drug validation in MesotheliomaKevin BlythCancer Research UK (CRUK)A29372Institute of Cancer Sciences