{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:30:50Z","timestamp":1790620250304,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,7,28]],"date-time":"2017-07-28T00:00:00Z","timestamp":1501200000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["P26011"],"award-info":[{"award-number":["P26011"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Castration\u2010resistant prostate cancer is a lethal disease. The cell type(s) that survive androgen deprivation remain poorly described, despite global efforts to understand the various mechanisms of therapy resistance. We recently identified in wild\u2010type (WT) mouse prostates a rare population of luminal progenitor cells that we called LSC<jats:sup>med<\/jats:sup> according to their FACS profile (Lin<jats:sup>\u2212<\/jats:sup>\/Sca\u20101<jats:sup>+<\/jats:sup>\/CD49f<jats:sup>med<\/jats:sup>). Here, we investigated the prevalence and castration resistance of LSC<jats:sup>med<\/jats:sup> in various mouse models of prostate tumourigenesis (Pb\u2010PRL, <jats:italic>Pten<\/jats:italic><jats:sup><jats:italic>pc\u2212\/\u2212<\/jats:italic><\/jats:sup>, and Hi\u2010Myc mice). LSC<jats:sup>med<\/jats:sup> prevalence is low (\u223c8%, similar to WT) in Hi\u2010Myc mice, where prostatic androgen receptor signalling is unaltered, but is significantly higher in the two other models, where androgen receptor signalling is decreased, rising up to more than 80% in <jats:italic>Pten<\/jats:italic><jats:sup><jats:italic>pc\u2212\/\u2212<\/jats:italic><\/jats:sup> prostates. LSC<jats:sup>med<\/jats:sup> tolerate androgen deprivation and persist or are enriched 2\u20133 weeks after castration. The tumour\u2010initiating properties of LSC<jats:sup>med<\/jats:sup> from <jats:italic>Pten<\/jats:italic><jats:sup><jats:italic>pc\u2212\/\u2212<\/jats:italic><\/jats:sup> mice were demonstrated by regeneration of tumours <jats:italic>in vivo<\/jats:italic>. Transcriptomic analysis revealed that LSC<jats:sup>med<\/jats:sup> represent a unique cell entity as their gene expression profile is different from luminal and basal\/stem cells, but shares markers of each. Their intrinsic androgen signalling is markedly decreased, explaining why LSC<jats:sup>med<\/jats:sup> tolerate androgen deprivation. This also illuminates why <jats:italic>Pten<\/jats:italic><jats:sup><jats:italic>pc\u2212\/\u2212<\/jats:italic><\/jats:sup> tumours are castration\u2010resistant since LSC<jats:sup>med<\/jats:sup> represent the most prevalent cell type in this model. We validated CK4 as a specific marker for LSC<jats:sup>med<\/jats:sup> on sorted cells and prostate tissues by immunostaining, allowing for the detection of LSC<jats:sup>med<\/jats:sup> in various mouse prostate specimens. In castrated <jats:italic>Pten<\/jats:italic><jats:sup><jats:italic>pc\u2212\/\u2212<\/jats:italic><\/jats:sup> prostates, there was significant proliferation of CK4<jats:sup>+<\/jats:sup> cells, further demonstrating their key role in castration\u2010resistant prostate cancer progression. Taken together, this study identifies LSC<jats:sup>med<\/jats:sup> as a probable source of prostate cancer relapse after androgen deprivation and as a new therapeutic target for the prevention of castrate\u2010resistant prostate cancer. Copyright \u00a9 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.4924","type":"journal-article","created":{"date-parts":[[2017,6,12]],"date-time":"2017-06-12T04:32:40Z","timestamp":1497241960000},"page":"51-64","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["A rare castration\u2010resistant progenitor cell population is highly enriched in Pten\u2010null prostate tumours"],"prefix":"10.1002","volume":"243","author":[{"given":"Lucila","family":"Sackmann Sala","sequence":"first","affiliation":[{"name":"Institut Necker Enfants Malades (INEM), Inserm U1151\u2013CNRS UMR 8253 University Paris Descartes, Sorbonne Paris Cit\u00e9, Faculty of Medicine  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Boutillon","sequence":"additional","affiliation":[{"name":"Institut Necker Enfants Malades (INEM), Inserm U1151\u2013CNRS UMR 8253 University Paris Descartes, Sorbonne Paris Cit\u00e9, Faculty of Medicine  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Menara","sequence":"additional","affiliation":[{"name":"Institut Necker Enfants Malades (INEM), Inserm U1151\u2013CNRS UMR 8253 University Paris Descartes, Sorbonne Paris Cit\u00e9, Faculty of Medicine  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9a","family":"De Goyon\u2010P\u00e9lard","sequence":"additional","affiliation":[{"name":"Institut Necker Enfants Malades (INEM), Inserm U1151\u2013CNRS UMR 8253 University Paris Descartes, Sorbonne Paris Cit\u00e9, Faculty of Medicine  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myl\u00e8ne","family":"Lepr\u00e9vost","sequence":"additional","affiliation":[{"name":"Institut Necker Enfants Malades (INEM), Inserm U1151\u2013CNRS UMR 8253 University Paris Descartes, Sorbonne Paris Cit\u00e9, Faculty of Medicine  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Codzamanian","sequence":"additional","affiliation":[{"name":"Institut Necker Enfants Malades (INEM), Inserm U1151\u2013CNRS UMR 8253 University Paris Descartes, Sorbonne Paris Cit\u00e9, Faculty of Medicine  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Lister","sequence":"additional","affiliation":[{"name":"Monash Partners Comprehensive Cancer Consortium and Cancer Program, Monash Biomedicine Discovery Institute, Prostate Cancer Research Group, Departments of Physiology and Anatomy and Developmental Biology Monash University  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Pencik","sequence":"additional","affiliation":[{"name":"Clinical Institute of Pathology Medical University of Vienna  Vienna Austria"},{"name":"Division of Nuclear Medicine, Department of Biomedical Imaging and Image\u2010Guided Therapy  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashlee","family":"Clark","sequence":"additional","affiliation":[{"name":"Monash Partners Comprehensive Cancer Consortium and Cancer Program, Monash Biomedicine Discovery Institute, Prostate Cancer Research Group, Departments of Physiology and Anatomy and Developmental Biology Monash University  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Cagnard","sequence":"additional","affiliation":[{"name":"Bioinformatics Core Facility, Inserm US 24\u2013CNRS UMS 3633\u2013SFR Necker University Paris Descartes, Sorbonne Paris Cit\u00e9, Faculty of Medicine  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Bole\u2010Feysot","sequence":"additional","affiliation":[{"name":"Genomics Core Facility, Inserm US 24\u2013CNRS UMS 3633\u2013SFR Necker University Paris Descartes, Sorbonne Paris Cit\u00e9, Faculty of Medicine  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Moriggl","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute for Cancer Research (LBI\u2010CR)  Vienna Austria"},{"name":"Institute of Animal Breeding and Genetics University of Veterinary Medicine Vienna, Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gail P","family":"Risbridger","sequence":"additional","affiliation":[{"name":"Monash Partners Comprehensive Cancer Consortium and Cancer Program, Monash Biomedicine Discovery Institute, Prostate Cancer Research Group, Departments of Physiology and Anatomy and Developmental Biology Monash University  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renea A","family":"Taylor","sequence":"additional","affiliation":[{"name":"Monash Partners Comprehensive Cancer Consortium and 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