{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T02:58:17Z","timestamp":1790132297561,"version":"4.0.1"},"reference-count":61,"publisher":"Bioscientifica","issue":"4","content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,8]]},"abstract":"<jats:p>\n                    Pituitary adenomas cause significant endocrine and mass-related morbidity. Little is known about the mechanisms that underlie pituitary tumor pathogenesis. In the present study, we searched for a side population (SP) in pituitary tumors representing cells with high efflux capacity and potentially enriched for tumor stem cells (TSCs). Human pituitary adenomas contain a SP irrespective of hormonal phenotype. This adenoma SP, as well as the purified SP (pSP) that is depleted from endothelial and immune cells, is enriched for cells that express \u2018tumor stemness\u2019 markers and signaling pathways, including epithelial\u2013mesenchymal transition (EMT)-linked factors. Pituitary adenomas were found to contain self-renewing sphere-forming cells, considered to be a property of TSCs. These sphere-initiating cells were recovered in the pSP. Because benign pituitary adenomas do not grow\n                    <jats:italic>in vitro<\/jats:italic>\n                    and have failed to expand in immunodeficient mice, the pituitary tumor cell line AtT20 was further used. We identified a SP in this cell line and found it to be more tumorigenic than the non-SP \u2018main population\u2019. Of the two EMT regulatory pathways tested, the inhibition of chemokine (C-X-C motif) receptor 4 (CXCR4) signaling reduced EMT-associated cell motility\n                    <jats:italic>in vitro<\/jats:italic>\n                    as well as xenograft tumor growth, whereas the activation of TGF\u03b2 had no effect. The human adenoma pSP also showed upregulated expression of the pituitary stem cell marker SOX2. Pituitaries from dopamine receptor D2 knockout (\n                    <jats:italic>Drd2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    ) mice that bear prolactinomas contain more pSP, Sox2\n                    <jats:sup>+<\/jats:sup>\n                    , and colony-forming cells than WT glands. In conclusion, we detected a SP in pituitary tumors and identified TSC-associated characteristics. The present study adds new elements to the unraveling of pituitary tumor pathogenesis and may lead to the identification of new therapeutic targets.\n                  <\/jats:p>","DOI":"10.1530\/erc-14-0546","type":"journal-article","created":{"date-parts":[[2015,4,28]],"date-time":"2015-04-28T21:22:26Z","timestamp":1430256146000},"page":"481-504","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":71,"title":["Pituitary tumors contain a side population with tumor stem cell-associated characteristics"],"prefix":"10.1530","volume":"22","author":[{"given":"Freya","family":"Mertens","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lies","family":"Gremeaux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianghai","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuli","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Willems","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heleen","family":"Roose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Govaere","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania","family":"Roskams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Cristina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damasia","family":"Bec\u00fa-Villalobos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Jorissen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent Vander","family":"Poorten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Bex","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"van Loon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo","family":"Vankelecom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"2015071018562120000_22.4.481.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2013.07.004"},{"key":"2015071018562120000_22.4.481.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2011.09.001"},{"key":"2015071018562120000_22.4.481.3","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-4717"},{"key":"2015071018562120000_22.4.481.4","doi-asserted-by":"publisher","DOI":"10.1038\/nature07602"},{"key":"2015071018562120000_22.4.481.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2009.06.006"},{"key":"2015071018562120000_22.4.481.6","doi-asserted-by":"publisher","DOI":"10.1038\/nature13305"},{"key":"2015071018562120000_22.4.481.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2012.03.041"},{"key":"2015071018562120000_22.4.481.8","doi-asserted-by":"publisher","DOI":"10.1210\/en.2005-0185"},{"key":"2015071018562120000_22.4.481.9","doi-asserted-by":"publisher","DOI":"10.1002\/stem.51"},{"key":"2015071018562120000_22.4.481.10","doi-asserted-by":"publisher","DOI":"10.1038\/nature11287"},{"key":"2015071018562120000_22.4.481.11","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2304"},{"key":"2015071018562120000_22.4.481.12","doi-asserted-by":"crossref","unstructured":"Cristina C Rubinstein M Low MJ Becu-Villalobos D 2006 Dopaminergic D2 receptor knockout mouse: an animal model of prolactinoma. 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