{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:05:39Z","timestamp":1792803939185,"version":"4.5.0"},"reference-count":65,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,11,13]],"date-time":"2020-11-13T00:00:00Z","timestamp":1605225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C1528\/A2690"],"award-info":[{"award-number":["C1528\/A2690"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Great 731 Britain Sasakawa Foundation","award":["B85"],"award-info":[{"award-number":["B85"]}],"id":[{"id":"https:\/\/ror.org\/021aawt29","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000388","name":"St Peter\u2019s Trust for Kidney Bladder &amp; Prostate Research","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100000388","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002089","name":"Fight for Sight","doi-asserted-by":"publisher","award":["F94"],"award-info":[{"award-number":["F94"]}],"id":[{"id":"10.13039\/100002089","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011702","name":"Childhood Eye Cancer Trust","doi-asserted-by":"publisher","award":["24CEC12"],"award-info":[{"award-number":["24CEC12"]}],"id":[{"id":"10.13039\/100011702","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Osteomodulin (OMD) and proline\/arginine-rich end leucine repeat protein (PRELP) are secreted extracellular matrix proteins belonging to the small leucine-rich proteoglycans family. We found that OMD and PRELP were specifically expressed in umbrella cells in bladder epithelia, and their expression levels were dramatically downregulated in all bladder cancers from very early stages and various epithelial cancers. Our in vitro studies including gene expression profiling using bladder cancer cell lines revealed that OMD or PRELP application suppressed the cancer progression by inhibiting TGF-\u03b2 and EGF pathways, which reversed epithelial\u2013mesenchymal transition (EMT), activated cell\u2013cell adhesion, and inhibited various oncogenic pathways. Furthermore, the overexpression of OMD in bladder cancer cells strongly inhibited the anchorage-independent growth and tumorigenicity in mouse xenograft studies. On the other hand, we found that in the bladder epithelia, the knockout mice of OMD and\/or PRELP gene caused partial EMT and a loss of tight junctions of the umbrella cells and resulted in formation of a bladder carcinoma in situ-like structure by spontaneous breakdowns of the umbrella cell layer. Furthermore, the ontological analysis of the expression profiling of an OMD knockout mouse bladder demonstrated very high similarity with those obtained from human bladder cancers. Our data indicate that OMD and PRELP are endogenous inhibitors of cancer initiation and progression by controlling EMT. OMD and\/or PRELP may have potential for the treatment of bladder cancer.<\/jats:p>","DOI":"10.3390\/cancers12113362","type":"journal-article","created":{"date-parts":[[2020,11,13]],"date-time":"2020-11-13T08:44:02Z","timestamp":1605257042000},"page":"3362","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Two Secreted Proteoglycans, Activators of Urothelial Cell\u2013Cell Adhesion, Negatively Contribute to Bladder Cancer Initiation and Progression"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6477-1627","authenticated-orcid":false,"given":"Vasiliki","family":"Papadaki","sequence":"first","affiliation":[{"name":"UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK"},{"name":"Institute of Fundamental Biological Research, Biomedical Sciences Research Center \u201cAlexander Fleming\u201d, 16672 Vari, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0548-4449","authenticated-orcid":false,"given":"Ken","family":"Asada","sequence":"additional","affiliation":[{"name":"Division of Molecular Modification and Cancer Biology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan"},{"name":"Cancer Translational Research Team, RIKEN Center for Advanced Intelligence Project, 1-4-1 Nihonbashi, Chuo-ku, Tokyo 103-0027, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1702-6085","authenticated-orcid":false,"given":"Julie K.","family":"Watson","sequence":"additional","affiliation":[{"name":"The Hutchison\/MRC Research Centre, Department of Oncology, University of Cambridge, Hills Road, Cambridge CB2 2XZ, UK"},{"name":"Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK"},{"name":"Stem Cell Technologies, Building 7100, 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