{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:19:39Z","timestamp":1791397179394,"version":"4.3.3"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,8,7]],"date-time":"2023-08-07T00:00:00Z","timestamp":1691366400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5U19CA214253"],"award-info":[{"award-number":["5U19CA214253"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000892","name":"Prostate Cancer Foundation","doi-asserted-by":"publisher","award":["19CHAS03"],"award-info":[{"award-number":["19CHAS03"]}],"id":[{"id":"10.13039\/100000892","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":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Club cells are a type of bronchiolar epithelial cell that serve a protective role in the lung and regenerate damaged lung epithelium. Single\u2010cell RNA sequencing (scRNA\u2010seq) of young adult human prostate and urethra identified cell populations in the prostatic urethra and collecting ducts similar in morphology and transcriptomic profile to lung club cells. We further identified club cell\u2010like epithelial cells by scRNA\u2010seq of prostate peripheral zone tissues. Here, we aimed to identify and spatially localize club cells\n                    <jats:italic>in situ<\/jats:italic>\n                    in the prostate, including in the peripheral zone. We performed chromogenic RNA\n                    <jats:italic>in situ<\/jats:italic>\n                    hybridization for five club cell markers (\n                    <jats:italic>CP<\/jats:italic>\n                    ,\n                    <jats:italic>LTF<\/jats:italic>\n                    ,\n                    <jats:italic>MMP7<\/jats:italic>\n                    ,\n                    <jats:italic>PIGR<\/jats:italic>\n                    ,\n                    <jats:italic>SCGB1A1<\/jats:italic>\n                    ) in a series of (1) nondiseased organ donor prostate and (2) radical prostatectomy specimens from individuals with prostate cancer. We report that expression of club cell genes in the peripheral zone is associated with inflammation and limited to luminal epithelial cells classified as intermediate cells in proliferative inflammatory atrophy (PIA). Club\u2010like cells were enriched in radical prostatectomy specimens compared to nondiseased prostates and associated with high\u2010grade prostate cancer. We previously reported that luminal epithelial cells in PIA can rarely harbor oncogenic\n                    <jats:italic>TMPRSS2:ERG<\/jats:italic>\n                    (ERG+) gene fusions, and we now demonstrate that club cells are present in association with ERG+ PIA that is transitioning to early adenocarcinoma. Finally, prostate epithelial organoids derived from prostatectomy specimens demonstrate that club\u2010like epithelial cells can be established in organoids and are sensitive to anti\u2010androgen\u2010directed treatment\n                    <jats:italic>in vitro<\/jats:italic>\n                    in terms of decreased androgen signaling gene expression signatures compared to basal or hillock cells. Overall, our study identifies a population of club\u2010like cells in PIA and proposes that these cells play an analogous role to that of club cells in bronchiolar epithelium. Our results further suggest that inflammation drives lineage plasticity in the human prostate and that club cells in PIA may be prone to oncogenic transformation. \u00a9 2023 The Authors.\n                    <jats:italic>The Journal of Pathology<\/jats:italic>\n                    published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.6149","type":"journal-article","created":{"date-parts":[[2023,8,7]],"date-time":"2023-08-07T23:46:57Z","timestamp":1691452017000},"page":"85-95","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Club\u2010like cells in proliferative inflammatory atrophy of the prostate"],"prefix":"10.1002","volume":"261","author":[{"given":"Franklin W","family":"Huang","sequence":"first","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine University of California  San Francisco CA USA"},{"name":"Helen Diller Family Comprehensive Cancer Center University of California  San Francisco CA USA"},{"name":"Department of Urology University of California  San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanbing","family":"Song","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine University of California  San Francisco CA USA"},{"name":"Helen Diller Family Comprehensive Cancer Center University of California  San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8409-4654","authenticated-orcid":false,"given":"Hannah NW","family":"Weinstein","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine University of California  San Francisco CA USA"},{"name":"Helen Diller Family Comprehensive Cancer Center University of California  San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie","family":"Xie","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine University of California  San Francisco CA USA"},{"name":"Helen Diller Family Comprehensive Cancer Center University of California  San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew R","family":"Cooperberg","sequence":"additional","affiliation":[{"name":"Department of Urology University of California  San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Hicks","sequence":"additional","affiliation":[{"name":"Department of Pathology Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke","family":"Mummert","sequence":"additional","affiliation":[{"name":"Department of Pathology Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo M","family":"De Marzo","sequence":"additional","affiliation":[{"name":"Department of Pathology Johns Hopkins University School of Medicine  Baltimore MD USA"},{"name":"Departments of Oncology and Urology Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7015-3059","authenticated-orcid":false,"given":"Karen S","family":"Sfanos","sequence":"additional","affiliation":[{"name":"Department of Pathology Johns Hopkins University School of Medicine  Baltimore MD USA"},{"name":"Departments of Oncology and Urology Johns Hopkins University School of Medicine  Baltimore MD 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