{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T20:56:00Z","timestamp":1780606560937,"version":"3.54.1"},"reference-count":41,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T00:00:00Z","timestamp":1731283200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22H03210"],"award-info":[{"award-number":["22H03210"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22K09466"],"award-info":[{"award-number":["22K09466"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020953","name":"Co-creation place formation support program","doi-asserted-by":"publisher","award":["JPMJPF2017"],"award-info":[{"award-number":["JPMJPF2017"]}],"id":[{"id":"10.13039\/501100020953","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The tumor microenvironment (TME) modulates therapeutic response and prognosis in patients with bladder cancer (BC). The roles of two phospholipase D (PLD) isoforms, PLD1 and PLD2 (hydrolysis of phosphatidylcholine to phosphatidic acid), in cancer cells have been well\u2010studied in numerous cancer types, but their roles in the TME remain unclear. We used a mouse BC <jats:italic>Pld2<\/jats:italic>\u2010KO carcinogenesis model and global transcriptomic analysis to reveal that PLD2 was significantly involved in BC progression through immunosuppressive pathways in the TME. We therefore focused on PLD2 and tumor\u2010associated macrophages (TAMs), which were increased in <jats:italic>Pld2<\/jats:italic>\u2010KO mice and further associated with poor prognoses in BC patients. In\u00a0vitro, we found that <jats:italic>Pld2<\/jats:italic>\u2010KO mouse TAMs had significantly enhanced proliferation, correlating closely with increased interleukin\u20101\u03b2 (IL\u20101\u03b2) production. These results indicate that PLD2 suppresses BC progression by regulation of IL\u20101\u03b2 secretion from TAMs in the TME, suggesting that PLD2 could serve as a potential therapeutic target for modifying the TME in BC.<\/jats:p>","DOI":"10.1111\/cas.16393","type":"journal-article","created":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T00:40:58Z","timestamp":1731372058000},"page":"381-392","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Phospholipase <scp>D2<\/scp> downregulates <scp>interleukin<\/scp>\u20101\u03b2 secretion from tumor\u2010associated macrophages to suppress bladder cancer progression"],"prefix":"10.1111","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-3905-7801","authenticated-orcid":false,"given":"Kazuki","family":"Hamada","sequence":"first","affiliation":[{"name":"Department of Urology, Faculty of Medicine University of Tsukuba  Tsukuba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiyuki","family":"Nagumo","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine University of Tsukuba  Tsukuba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4621-8470","authenticated-orcid":false,"given":"Shuya","family":"Kandori","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine University of Tsukuba  Tsukuba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bunpei","family":"Isoda","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine University of Tsukuba  Tsukuba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhei","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine University of Tsukuba  Tsukuba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Sano","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine University of Tsukuba  Tsukuba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shotaro","family":"Sakka","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine University of Tsukuba  Tsukuba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1748-4825","authenticated-orcid":false,"given":"Kozaburo","family":"Tanuma","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine University of Tsukuba  Tsukuba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2855-1061","authenticated-orcid":false,"given":"Satoshi","family":"Nitta","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine University of Tsukuba  Tsukuba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanobu","family":"Shiga","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine University of Tsukuba  Tsukuba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromitsu","family":"Negoro","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine University of Tsukuba  Tsukuba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan J.","family":"Mathis","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Faculty of Medicine University of Tsukuba  Tsukuba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Funakoshi","sequence":"additional","affiliation":[{"name":"Department of Physiological Chemistry, Faculty of Medicine University of Tsukuba  Tsukuba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7423-596X","authenticated-orcid":false,"given":"Hiroyuki","family":"Nishiyama","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine University of Tsukuba  Tsukuba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,11]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_10_3_1","doi-asserted-by":"crossref","DOI":"10.1136\/bmj-2023-076743","article-title":"Advances in diagnosis and treatment of bladder cancer","volume":"384","author":"Lopez\u2010Beltran A","year":"2024","journal-title":"BMJ"},{"key":"e_1_2_10_4_1","first-page":"8","article-title":"Epidemiology of bladder cancer","volume":"8","author":"Saginala K","year":"2020","journal-title":"Med Sci (Basel)"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1701990"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.21471"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16091626"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.06.016"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.50.29640"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.21.12846"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.114.009217"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2013.207"},{"key":"e_1_2_10_13_1","first-page":"1329","article-title":"Expression of phospholipase D2 in human colorectal carcinoma","volume":"18","author":"Saito M","year":"2007","journal-title":"Oncol Rep"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2018.03.006"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.3719"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-24512-x"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2021.04.014"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0805177106"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01286"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.203613"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0209196"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp1607591"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa407"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00229.2017"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1822001116"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13020288"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.613170"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-14-480"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.110309"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12071791"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21176009"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-020-07548-z"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.30224"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.2.645-654.2003"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M600660200"},{"key":"e_1_2_10_36_1","first-page":"789","article-title":"Phospholipase D in cell proliferation and cancer","volume":"1","author":"Foster DA","year":"2003","journal-title":"Mol Cancer Res"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-10-2463"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232113286"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40164-021-00252-z"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-21-3603"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13184712"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-18-3208"}],"container-title":["Cancer Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.16393","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.16393","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T13:44:32Z","timestamp":1738417472000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cas.16393"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,11]]},"references-count":41,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1111\/cas.16393"],"URL":"https:\/\/doi.org\/10.1111\/cas.16393","archive":["Portico"],"relation":{},"ISSN":["1347-9032","1349-7006"],"issn-type":[{"value":"1347-9032","type":"print"},{"value":"1349-7006","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,11]]},"assertion":[{"value":"2024-07-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}