{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T02:44:10Z","timestamp":1789267450227,"version":"build-2803163510"},"reference-count":51,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,4,3]],"date-time":"2017-04-03T00:00:00Z","timestamp":1491177600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u2018Ministerio de Econom\u00eda y Competitividad\u2019\/Fondo Europeo de Desarrollo Regional (MINECO\/FEDER)","award":["SAF2013-47611R"],"award-info":[{"award-number":["SAF2013-47611R"]}]},{"name":"\u2018Ministerio de Econom\u00eda y Competitividad\u2019\/Fondo Europeo de Desarrollo Regional (MINECO\/FEDER)","award":["SAF2016-80648R"],"award-info":[{"award-number":["SAF2016-80648R"]}]},{"DOI":"10.13039\/100012818","name":"Comunidad Aut\u00f3noma de Madrid","doi-asserted-by":"crossref","award":["S2010\/BMD-2321"],"award-info":[{"award-number":["S2010\/BMD-2321"]}],"id":[{"id":"10.13039\/100012818","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Institute of Health, the US Department of Health and Human Services","award":["R01CA169200"],"award-info":[{"award-number":["R01CA169200"]}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2017,6]]},"abstract":"Abstract<\/jats:title>\n \n Peritoneal dissemination is the primary metastatic route of ovarian cancer (\n OvCa<\/jats:styled-content>\n ), and is often accompanied by the accumulation of ascitic fluid. The peritoneal cavity is lined by mesothelial cells (\n MCs<\/jats:styled-content>\n ), which can be converted into carcinoma\u2010associated fibroblasts (\n CAFs<\/jats:styled-content>\n ) through mesothelial\u2010to\u2010mesenchymal transition (\n MMT<\/jats:styled-content>\n ). Here, we demonstrate that\n MCs<\/jats:styled-content>\n isolated from ascitic fluid (\n AFMCs<\/jats:styled-content>\n ) of\n OvCa<\/jats:styled-content>\n patients with peritoneal implants also undergo\n MMT<\/jats:styled-content>\n and promote subcutaneous tumour growth in mice.\n RNA<\/jats:styled-content>\n sequencing of\n AFMCs<\/jats:styled-content>\n revealed that\n MMT<\/jats:styled-content>\n \u2010related pathways\u00a0\u2013\u00a0including transforming growth factor (\n TGF<\/jats:styled-content>\n )\u2010\u03b2 signalling\u00a0\u2013\u00a0are differentially regulated, and a gene signature was verified in peritoneal implants from\n OvCa<\/jats:styled-content>\n patients. In a mouse model, pre\u2010induction of\n MMT<\/jats:styled-content>\n resulted in increased peritoneal tumour growth, whereas interfering with the\n TGF<\/jats:styled-content>\n \u2010\u03b2 receptor reduced metastasis.\n MC<\/jats:styled-content>\n \u2010derived\n CAFs<\/jats:styled-content>\n showed activation of Smad\u2010dependent\n TGF<\/jats:styled-content>\n \u2010\u03b2 signalling, which was disrupted in\n OvCa<\/jats:styled-content>\n cells, despite their elevated\n TGF<\/jats:styled-content>\n \u2010\u03b2 production. Accordingly, targeting Smad\u2010dependent signalling in the peritoneal pre\u2010metastatic niche in mice reduced tumour colonization, suggesting that Smad\u2010dependent\n MMT<\/jats:styled-content>\n could be crucial in peritoneal carcinomatosis. Together, these results indicate that bidirectional communication between\n OvCa<\/jats:styled-content>\n cells and\n MC<\/jats:styled-content>\n \u2010derived\n CAFs<\/jats:styled-content>\n , via\n TGF<\/jats:styled-content>\n \u2010\u03b2\u2010mediated\n MMT<\/jats:styled-content>\n , seems to be crucial to form a suitable metastatic niche. We suggest\n MMT<\/jats:styled-content>\n as a possible target for therapeutic intervention and a potential source of biomarkers for improving\n OvCa<\/jats:styled-content>\n diagnosis and\/or prognosis. \u00a9 2017 The Authors.\n The Journal of Pathology<\/jats:italic>\n published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.\n <\/jats:p>","DOI":"10.1002\/path.4889","type":"journal-article","created":{"date-parts":[[2017,3,1]],"date-time":"2017-03-01T04:39:55Z","timestamp":1488343195000},"page":"140-151","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":107,"title":["Mesothelial\u2010to\u2010mesenchymal transition as a possible therapeutic target in peritoneal metastasis of ovarian cancer"],"prefix":"10.1002","volume":"242","author":[{"given":"Angela","family":"Rynne\u2010Vidal","sequence":"first","affiliation":[{"name":"Centro de Biolog\u00eda Molecular\u2010Severo Ochoa (CBMSO) 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Molecular\u2010Severo Ochoa (CBMSO) Departamento de Biolog\u00eda Celular e Inmunolog\u00eda Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc\u00eda","family":"Cremades\u2010Jimeno","sequence":"additional","affiliation":[{"name":"Centro de Biolog\u00eda Molecular\u2010Severo Ochoa (CBMSO) Departamento de Biolog\u00eda Celular e Inmunolog\u00eda Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"B\u00e1rcena","sequence":"additional","affiliation":[{"name":"Departamento de Anatom\u00eda Patol\u00f3gica Hospital Universitario 12 de Octubre Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignacio","family":"Crist\u00f3bal\u2010Garc\u00eda","sequence":"additional","affiliation":[{"name":"Servicio de Oncolog\u00eda Ginecol\u00f3gica Hospital de la Zarzuela Sanitas Madrid 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