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Our recent studies showed that expression of endothelial cell protein C receptor (EPCR) in MPM cells suppresses tumorigenicity. The present study was aimed to investigate the mechanism by which EPCR suppresses MPM tumor growth and evaluate whether EPCR gene therapy could suppress the progression of MPM in a mouse model of MPM. Measurement of cytokines from the pleural lavage showed that mice implanted with MPM cells expressing EPCR had elevated levels of IFN\u03b3 and TNF\u03b1 compared to mice implanted with MPM cells lacking EPCR. <jats:italic>In vitro<\/jats:italic> studies demonstrated that EPCR expression renders MPM cells highly susceptible to IFN\u03b3\u2009+\u2009TNF\u03b1-induced apoptosis. Intrapleural injection of Ad.EPCR into mice with an established MPM originating from MPM cells lacking EPCR reduced the progression of tumor growth. Ad.EPCR treatment elicited recruitment of macrophages and NK cells into the tumor microenvironment and increased IFN\u03b3 and TNF\u03b1 levels in the pleural space. Ad.EPCR treatment resulted in a marked increase in tumor cell apoptosis. In summary, our data show that EPCR expression in MPM cells promotes tumor cell apoptosis, and intrapleural EPCR gene therapy suppresses MPM progression.<\/jats:p>","DOI":"10.1038\/srep36829","type":"journal-article","created":{"date-parts":[[2016,11,11]],"date-time":"2016-11-11T09:57:25Z","timestamp":1478858245000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Intrapleural Adenoviral-mediated Endothelial Cell Protein C Receptor Gene Transfer Suppresses the Progression of Malignant Pleural Mesothelioma in a Mouse Model"],"prefix":"10.1038","volume":"6","author":[{"given":"Shiva","family":"Keshava","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. 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