{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T04:29:54Z","timestamp":1770524994084,"version":"3.49.0"},"reference-count":44,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,1,28]],"date-time":"2024-01-28T00:00:00Z","timestamp":1706400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"JSPS (Japan Society for the Promotion of Science) KAKENHI Grants-in-Aid for Scientific Research","doi-asserted-by":"publisher","award":["20H03824"],"award-info":[{"award-number":["20H03824"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"JSPS (Japan Society for the Promotion of Science) KAKENHI Grants-in-Aid for Scientific Research","doi-asserted-by":"publisher","award":["21KK0296"],"award-info":[{"award-number":["21KK0296"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"JSPS (Japan Society for the Promotion of Science) KAKENHI Grants-in-Aid for Scientific Research","doi-asserted-by":"publisher","award":["21K09492"],"award-info":[{"award-number":["21K09492"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"JSPS (Japan Society for the Promotion of Science) KAKENHI Grants-in-Aid for Scientific Research","doi-asserted-by":"publisher","award":["21KK0157"],"award-info":[{"award-number":["21KK0157"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"JSPS (Japan Society for the Promotion of Science) KAKENHI Grants-in-Aid for Scientific Research","doi-asserted-by":"publisher","award":["21K16788"],"award-info":[{"award-number":["21K16788"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Most epithelial ovarian cancer (EOC) patients are diagnosed with peritoneal dissemination. Cellular interactions are an important aspect of EOC cells when they detach from the primary site of the ovary. However, the mechanism remains underexplored. Our study aimed to reveal the role of chondroitin sulfate proteoglycan 4 (CSPG4) in EOC with a major focus on cell\u2013cell interactions. We examined the expression of CSPG4 in clinical samples and cell lines of EOC. The proliferation, migration, and invasion abilities of the CSPG4 knockdown cells were assessed. We also assessed the role of CSPG4 in spheroid formation and peritoneal metastasis in an in vivo model using sh-CSPG4 EOC cell lines. Of the clinical samples, 23 (44.2%) samples expressed CSPG4. CSPG4 was associated with a worse prognosis in patients with advanced EOC. Among the EOC cell lines, aggressive cell lines, including ES2, expressed CSPG4. When CSPG4 was knocked down using siRNA or shRNA, the cell proliferation, migration, and invasion abilities were significantly decreased compared to the control cells. Proteomic analyses showed changes in the expression of proteins related to the cell movement pathways. Spheroid formation was significantly inhibited when CSPG4 was inhibited. The number of nodules and the tumor burden of the omentum were significantly decreased in the sh-CSPG4 mouse models. In the peritoneal wash fluid from mice injected with sh-CSPG4 EOC cells, significantly fewer spheroids were present. Reduced CSPG4 expression was observed in lymphoid enhancer-binding factor 1-inhibited cells. CSPG4 is associated with aggressive features of EOC and poor prognosis. CSPG4 could be a new treatment target for blocking peritoneal metastasis by inhibiting spheroid formation.<\/jats:p>","DOI":"10.3390\/ijms25031626","type":"journal-article","created":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T08:11:27Z","timestamp":1706515887000},"page":"1626","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Chondroitin Sulfate Proteoglycan 4 Provides New Treatment Approach to Preventing Peritoneal Dissemination in Ovarian Cancer"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7762-5039","authenticated-orcid":false,"given":"Kaname","family":"Uno","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Aichi, Japan"},{"name":"Division of Clinical Genetics, Department of Laboratory Medicine, Lund University Graduate School of Medicine, 22184 Lund Postcode City, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4505-8778","authenticated-orcid":false,"given":"Yoshihiro","family":"Koya","sequence":"additional","affiliation":[{"name":"Bell Research Center, Department of Obstetrics and Gynecology Collaborative Research, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Aichi, Japan"},{"name":"Bell Research Center for Reproductive Health and Cancer, Medical Corporation Kishokai, Nagoya 466-8550, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5811-3137","authenticated-orcid":false,"given":"Masato","family":"Yoshihara","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shohei","family":"Iyoshi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Aichi, Japan"},{"name":"Spemann Graduate School of Biology and Medicine, University of Freiburg, 79104 Freiburg, Germany"},{"name":"Institute for Advanced Research, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9691-4728","authenticated-orcid":false,"given":"Kazuhisa","family":"Kitami","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Aichi, Japan"},{"name":"Department of Obstetrics and Gynecology, Kitasato University School of Medicine, Sagamihara 252-0375, Kanagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mai","family":"Sugiyama","sequence":"additional","affiliation":[{"name":"Bell Research Center, Department of Obstetrics and Gynecology Collaborative Research, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Aichi, Japan"},{"name":"Bell Research Center for Reproductive Health and Cancer, Medical Corporation Kishokai, Nagoya 466-8550, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emiri","family":"Miyamoto","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazumasa","family":"Mogi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5659-1362","authenticated-orcid":false,"given":"Hiroki","family":"Fujimoto","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Aichi, Japan"},{"name":"Discipline of Obstetrics and Gynecology, Adelaide Medical School, Robinson Research Institute, University of Adelaide, Adelaide 5000, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshihiko","family":"Yamakita","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Aichi, Japan"},{"name":"Bell Research Center, Department of Obstetrics and Gynecology Collaborative Research, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Aichi, Japan"},{"name":"Bell Research Center for Reproductive Health and 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