{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T01:27:33Z","timestamp":1785547653965,"version":"3.56.0"},"reference-count":29,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T00:00:00Z","timestamp":1668643200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004622","name":"KWF Kankerbestrijding","doi-asserted-by":"publisher","award":["10496"],"award-info":[{"award-number":["10496"]}],"id":[{"id":"10.13039\/501100004622","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008359","name":"Maag Lever Darm Stichting","doi-asserted-by":"publisher","award":["D16\u201026"],"award-info":[{"award-number":["D16\u201026"]}],"id":[{"id":"10.13039\/501100008359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2023,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease of the biliary tree and a risk factor for development of cholangiocarcinoma (CCA). The pathogenesis of PSC\u2010related CCA is largely unclear, although it is assumed that chronic inflammatory environment plays a pivotal role. We aimed to investigate the effect of inflammation\u2010related cytokines in PSC on the proliferation rate of cancer cells. For this, the proliferation index in PSC\u2010CCA and sporadic CCA was determined by Ki\u201067 immunohistochemistry. The percentage of Ki\u201067 positivity in cancer cells was significantly higher in PSC\u2010CCA than in sporadic CCA (41.3%\u2009\u00b1\u20095.7% vs 25.8%\u2009\u00b1\u20094.1%; <jats:italic>P<\/jats:italic>\u00a0=\u00a0.038). To assess which cytokines in the inflammatory environment have the potential to stimulate cancer cell proliferation, patient\u2010derived CCA organoids (CCAOs) were exposed to five cytokines related to PSC (Interleukin (IL)\u20101\u03b2, IL\u20106, IL\u201017A, interferon gamma and tumor necrosis factor alpha). Only IL\u201017A showed a significant stimulatory effect on cell proliferation in CCAOs, increasing organoid size by 45.9%\u2009\u00b1\u200916.4% (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.01) and proliferation rate by 38%\u2009\u00b1\u200916% (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.05). IL\u201017A immunohistochemistry demonstrated that PSC\u2010CCA might express more IL\u201017A than sporadic CCA. Moreover, correlation analysis in sporadic CCA and PSC\u2010CCA found a significant correlation between IL\u201017A expression and proliferation. In conclusion, tumor cell proliferation is increased in PSC\u2010CCA cells compared with sporadic CCA cells. IL\u201017A increases CCA cell proliferation in vitro and may contribute to the high proliferation rate in PSC\u2010CCA in situ. Therefore, IL\u201017A represents a new potential therapeutic target in (PSC\u2010)CCA, to be tested in future trials.<\/jats:p>","DOI":"10.1002\/ijc.34350","type":"journal-article","created":{"date-parts":[[2022,11,8]],"date-time":"2022-11-08T12:40:50Z","timestamp":1667911250000},"page":"2607-2614","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Cholangiocarcinoma cell proliferation is enhanced in primary sclerosing cholangitis: A role for <scp>IL\u201017A<\/scp>"],"prefix":"10.1002","volume":"152","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7848-3933","authenticated-orcid":false,"given":"Ruby","family":"Lieshout","sequence":"first","affiliation":[{"name":"Department of Surgery, Erasmus MC Transplant Institute, Erasmus MC University Medical Center  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5410-9878","authenticated-orcid":false,"given":"Eline J. C. A.","family":"Kamp","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9908-6673","authenticated-orcid":false,"given":"Monique M. A.","family":"Verstegen","sequence":"additional","affiliation":[{"name":"Department of Surgery, Erasmus MC Transplant Institute, Erasmus MC University Medical Center  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michail","family":"Doukas","sequence":"additional","affiliation":[{"name":"Department of Pathology, Erasmus MC Cancer Institute, Erasmus MC University Medical Center  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winand N. M.","family":"Dinjens","sequence":"additional","affiliation":[{"name":"Department of Pathology, Erasmus MC Cancer Institute, Erasmus MC University Medical Center  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K\u00fcbra","family":"K\u00f6ten","sequence":"additional","affiliation":[{"name":"Department of Surgery, Erasmus MC Transplant Institute, Erasmus MC University Medical Center  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan N. M.","family":"IJzermans","sequence":"additional","affiliation":[{"name":"Department of Surgery, Erasmus MC Transplant Institute, Erasmus MC University Medical Center  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco J.","family":"Bruno","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maikel P.","family":"Peppelenbosch","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc J. 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