{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T22:39:28Z","timestamp":1791412768055,"version":"4.3.3"},"reference-count":38,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,5,8]],"date-time":"2014-05-08T00:00:00Z","timestamp":1399507200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2014,6]]},"abstract":"<jats:p>Cholangiocarcinoma is an aggressive malignant tumor originating from intrahepatic or extrahepatic bile ducts. Its malignant phenotypes may be assumed by cancer stem cells (<jats:styled-content style=\"fixed-case\">CSC<\/jats:styled-content>). Here, we demonstrate that <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>274 (<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u2010L1), known as an immunomodulatory ligand, has suppressive effects on <jats:styled-content style=\"fixed-case\">CSC<\/jats:styled-content>\u2010related phenotypes of cholangiocarcinoma. Using two human cholangiocarcinoma cell lines, <jats:styled-content style=\"fixed-case\">RBE<\/jats:styled-content> and Hu<jats:styled-content style=\"fixed-case\">CCT<\/jats:styled-content>1, we attempted to isolate the <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>274<jats:sup>low<\/jats:sup> and <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>274<jats:sup>high<\/jats:sup> cells from each cell line, and xenografted them into immunodeficient <jats:styled-content style=\"fixed-case\">NOD<\/jats:styled-content>\u2044scid\u2044\u03b3cnull (<jats:styled-content style=\"fixed-case\">NOG<\/jats:styled-content>) mice. We found that the <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>274<jats:sup>low<\/jats:sup> cells isolated from both <jats:styled-content style=\"fixed-case\">RBE<\/jats:styled-content> and Hu<jats:styled-content style=\"fixed-case\">CCT<\/jats:styled-content>1 are highly tumorigenic in <jats:styled-content style=\"fixed-case\">NOG<\/jats:styled-content> mice compared with <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>274<jats:sup>high<\/jats:sup> cells. Furthermore, the <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>274<jats:sup>low<\/jats:sup> cells possess several <jats:styled-content style=\"fixed-case\">CSC<\/jats:styled-content>\u2010related characteristics, such as high <jats:styled-content style=\"fixed-case\">aldehyde dehydrogenase (ALDH)<\/jats:styled-content> activity, reduced reactive oxygen species production and a dormant state in the cell cycle. Furthermore, depletion of CD274 expression by sh<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">RBE<\/jats:styled-content> cells enhances their tumorigenicity and increases <jats:styled-content style=\"fixed-case\">ALDH<\/jats:styled-content> activity. These findings are compatible with our observation that clinical cholangiocarcinoma specimens are classified into low and high groups for <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>274 expression, and the <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>274 low group shows poorer prognosis when compared with the <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>274 high group. These results strongly suggest that <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>274 has a novel function in the negative regulation of <jats:styled-content style=\"fixed-case\">CSC<\/jats:styled-content>\u2010related phenotypes in human cholangiocarcinoma, which is distinct from its immunomodulatory actions.<\/jats:p>","DOI":"10.1111\/cas.12406","type":"journal-article","created":{"date-parts":[[2014,3,27]],"date-time":"2014-03-27T03:42:53Z","timestamp":1395891773000},"page":"667-674","source":"Crossref","is-referenced-by-count":44,"title":["Suppressive expression of <scp>CD<\/scp>274 increases tumorigenesis and cancer stem cell phenotypes in cholangiocarcinoma"],"prefix":"10.1111","volume":"105","author":[{"given":"Keiichi","family":"Tamai","sequence":"first","affiliation":[{"name":"Division of Cancer Biology and Therapeutics Miyagi Cancer Center Research Institute Natori Japan"},{"name":"Department of Cancer Science Tohoku University Graduate School of Medicine 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