{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T19:20:51Z","timestamp":1789932051968,"version":"4.0.1"},"reference-count":57,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T00:00:00Z","timestamp":1666051200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"UKRI Medical Research Council","award":["MC_UU_00025\/5\/MRC_\/Medical Research Council\/United Kingdom"],"award-info":[{"award-number":["MC_UU_00025\/5\/MRC_\/Medical Research Council\/United Kingdom"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Malignant mesothelioma is an aggressive tumour of the pleura (MPM) or peritoneum with a clinical presentation at an advanced stage of the disease. Current therapies only marginally improve survival and there is an urgent need to identify new treatments. Carcinoma-associated fibroblasts (CAFs) represent the main component of a vast stroma within MPM and play an important role in the tumour microenvironment. The influence of CAFs on cancer progression, aggressiveness and metastasis is well understood; however, the role of CAF-derived extracellular vesicles (CAF-EVs) in the promotion of tumour development and invasiveness is underexplored. We purified CAF-EVs from MPM-associated cells and healthy dermal human fibroblasts and examined their effect on cell proliferation and motility. The data show that exposure of healthy mesothelial cells to EVs derived from CAFs, but not from normal dermal human fibroblasts (NDHF) resulted in activating pro-oncogenic signalling pathways and increased proliferation and motility. Consistent with its role in suppressing Yes-Associated Protein (YAP) activation (which in MPM is a result of Hippo pathway inactivation), treatment with Simvastatin ameliorated the pro-oncogenic effects instigated by CAF-EVs by mechanisms involving both a reduction in EV number and changes in EV cargo. Collectively, these data determine the significance of CAF-derived EVs in mesothelioma development and progression and suggest new targets in cancer therapy.<\/jats:p>","DOI":"10.3390\/ijms232012469","type":"journal-article","created":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T21:18:02Z","timestamp":1666127882000},"page":"12469","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Extracellular Vesicles Isolated from Malignant Mesothelioma Cancer-Associated Fibroblasts Induce Pro-Oncogenic Changes in Healthy Mesothelial Cells"],"prefix":"10.3390","volume":"23","author":[{"given":"Tatyana","family":"Chernova","sequence":"first","affiliation":[{"name":"MRC Toxicology Unit, University of Cambridge, Tennis Court Rd., Cambridge CB2 1QR, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Grosso","sequence":"additional","affiliation":[{"name":"MRC Toxicology Unit, University of Cambridge, Tennis Court Rd., Cambridge CB2 1QR, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Ming","family":"Sun","sequence":"additional","affiliation":[{"name":"MRC Toxicology Unit, University of Cambridge, Tennis Court Rd., Cambridge CB2 1QR, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela Rubio","family":"Tenor","sequence":"additional","affiliation":[{"name":"MRC Toxicology Unit, University of Cambridge, Tennis Court Rd., Cambridge CB2 1QR, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaquin Zacarias","family":"Cabeza","sequence":"additional","affiliation":[{"name":"MRC Toxicology Unit, University of Cambridge, Tennis Court Rd., Cambridge CB2 1QR, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Craxton","sequence":"additional","affiliation":[{"name":"MRC Toxicology Unit, University of Cambridge, Tennis Court Rd., Cambridge CB2 1QR, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily L.","family":"Self","sequence":"additional","affiliation":[{"name":"MRC Toxicology Unit, University of Cambridge, Tennis Court Rd., Cambridge CB2 1QR, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apostolos","family":"Nakas","sequence":"additional","affiliation":[{"name":"UHL NHS Trust, Glenfield Hospital, Leicester LE3 9QP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelvin","family":"Cain","sequence":"additional","affiliation":[{"name":"MRC Toxicology Unit, University of Cambridge, Tennis Court Rd., Cambridge CB2 1QR, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7886-1159","authenticated-orcid":false,"given":"Marion","family":"MacFarlane","sequence":"additional","affiliation":[{"name":"MRC Toxicology Unit, University of Cambridge, Tennis Court Rd., Cambridge CB2 1QR, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1470-8531","authenticated-orcid":false,"given":"Anne E.","family":"Willis","sequence":"additional","affiliation":[{"name":"MRC Toxicology Unit, University of Cambridge, Tennis Court Rd., Cambridge CB2 1QR, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.rmed.2017.11.015","article-title":"Progress and challenges in Mesothelioma: From bench to bedside","volume":"134","author":"Blyth","year":"2018","journal-title":"Respir. 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