{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:29:28Z","timestamp":1791404968468,"version":"4.3.3"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,4,12]],"date-time":"2017-04-12T00:00:00Z","timestamp":1491955200000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"National Institute of Biomedical Innovation (NIBIO)"},{"name":"Scientific Research in Innovative Areas"},{"name":"Network for Integrative Research on Cancer Microenvironments of the Ministry of Education, Culture, Sports, Science, and Technology of Japan"},{"name":"JSPS KAKENHI","award":["16H05308"],"award-info":[{"award-number":["16H05308"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2017,4]]},"abstract":"<jats:p>Malignant pleural mesothelioma (<jats:styled-content style=\"fixed-case\">MPM<\/jats:styled-content>) is characterized by dissemination and aggressive growth in the thoracic cavity. Podoplanin (<jats:styled-content style=\"fixed-case\">PDPN<\/jats:styled-content>) is an established diagnostic marker for <jats:styled-content style=\"fixed-case\">MPM<\/jats:styled-content>, but the function of <jats:styled-content style=\"fixed-case\">PDPN<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">MPM<\/jats:styled-content> is not fully understood. The purpose of this study was to determine the pathogenetic function of <jats:styled-content style=\"fixed-case\">PDPN<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">MPM<\/jats:styled-content>. Forty\u2010seven of 52 tumors (90%) from Japanese patients with <jats:styled-content style=\"fixed-case\">MPM<\/jats:styled-content> and 3\/6 (50%) <jats:styled-content style=\"fixed-case\">MPM<\/jats:styled-content> cell lines tested positive for <jats:styled-content style=\"fixed-case\">PDPN<\/jats:styled-content>. Knocking down <jats:styled-content style=\"fixed-case\">PDPN<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">PDPN<\/jats:styled-content>\u2010high expressing <jats:styled-content style=\"fixed-case\">MPM<\/jats:styled-content> cells resulted in decreased cell motility. In contrast, overexpression of <jats:styled-content style=\"fixed-case\">PDPN<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">PDPN<\/jats:styled-content>\u2010low expressing <jats:styled-content style=\"fixed-case\">MPM<\/jats:styled-content> cells enhanced cell motility. <jats:styled-content style=\"fixed-case\">PDPN<\/jats:styled-content> stimulated motility was mediated by activation of the RhoA\/<jats:styled-content style=\"fixed-case\">ROCK<\/jats:styled-content> pathway. Moreover, knocking down <jats:styled-content style=\"fixed-case\">PDPN<\/jats:styled-content> with short hairpin (sh) <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">PDPN<\/jats:styled-content>\u2010high expressing <jats:styled-content style=\"fixed-case\">MPM<\/jats:styled-content> cells resulted in decreased development of a thoracic tumor in mice with severe combined immune deficiency (<jats:styled-content style=\"fixed-case\">SCID<\/jats:styled-content>). In sharp contrast, transfection of <jats:styled-content style=\"fixed-case\">PDPN<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">PDPN<\/jats:styled-content>\u2010low expressing <jats:styled-content style=\"fixed-case\">MPM<\/jats:styled-content> cells resulted in an increase in the number of Ki\u201067\u2010positive proliferating tumor cells and it promoted progression of a thoracic tumor in <jats:styled-content style=\"fixed-case\">SCID<\/jats:styled-content> mice. Interestingly, <jats:styled-content style=\"fixed-case\">PDPN<\/jats:styled-content> promoted focus formation <jats:italic>in\u00a0vitro<\/jats:italic>, and a low level of E\u2010cadherin expression and <jats:styled-content style=\"fixed-case\">YAP<\/jats:styled-content>1 activation was observed in <jats:styled-content style=\"fixed-case\">PDPN<\/jats:styled-content>\u2010high <jats:styled-content style=\"fixed-case\">MPM<\/jats:styled-content> tumors. These findings indicate that <jats:styled-content style=\"fixed-case\">PDPN<\/jats:styled-content> is a diagnostic marker as well as a pathogenetic regulator that promotes <jats:styled-content style=\"fixed-case\">MPM<\/jats:styled-content> progression by increasing cell motility and inducing focus formation. Therefore, <jats:styled-content style=\"fixed-case\">PDPN<\/jats:styled-content> might be a pathogenetic determinant of <jats:styled-content style=\"fixed-case\">MPM<\/jats:styled-content> dissemination and aggressive growth and may thus be an ideal therapeutic target.<\/jats:p>","DOI":"10.1111\/cas.13190","type":"journal-article","created":{"date-parts":[[2017,2,9]],"date-time":"2017-02-09T15:06:44Z","timestamp":1486652804000},"page":"696-703","source":"Crossref","is-referenced-by-count":19,"title":["Podoplanin promotes progression of malignant pleural mesothelioma by regulating motility and focus formation"],"prefix":"10.1111","volume":"108","author":[{"given":"Shinji","family":"Takeuchi","sequence":"first","affiliation":[{"name":"Division of Medical Oncology Cancer Research Institute Kanazawa University Kanazawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Fukuda","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology 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