{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T11:03:12Z","timestamp":1793876592433,"version":"4.7.0"},"reference-count":55,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2020,1,24]],"date-time":"2020-01-24T00:00:00Z","timestamp":1579824000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["16K15704"],"award-info":[{"award-number":["16K15704"]}],"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":["17H04338"],"award-info":[{"award-number":["17H04338"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2020,4,15]]},"abstract":"<jats:p>Peritoneal dissemination of ovarian cancer (OvCa) arises from the surface of the peritoneum, covered by monolayer of mesothelial cells (MCs). Given that both OvCa cells and MCs are present in the same peritoneal metastatic microenvironment, they may establish cell\u2010to\u2010cell crosstalk or phenotypic alterations including the acquisition of platinum\u2010resistance in OvCa cells. Herein, we report how OvCa\u2010associated mesothelial cells (OCAMs) induce platinum\u2010resistance in OvCa cells through direct cell\u2010to\u2010cell crosstalk. We evaluated mutual associations between OvCa cells and human primary MCs with <jats:italic>in vitro<\/jats:italic> coculturing experimental models and <jats:italic>in silico<\/jats:italic> omics data analysis. The role of OCAMs was also investigated using clinical samples and <jats:italic>in vivo<\/jats:italic> mice models. Results of <jats:italic>in vitro<\/jats:italic> experiments show that mesenchymal transition is induced in OCAMs primarily by TGF\u2010\u03b21 stimulation. Furthermore, OCAMs influence the behavior of OvCa cells as a component of the tumor microenvironment of peritoneal metastasis. Mechanistically, OCAMs can induce decreased platinum\u2010sensitivity in OvCa cells <jats:italic>via<\/jats:italic> induction of the FN1\/Akt signaling pathway <jats:italic>via<\/jats:italic> cell\u2010to\u2010cell interactions. Histological analysis of OvCa peritoneal metastasis also illustrated FN1 expression in stromal cells that are supposed to originate from MCs. Further, we also confirmed the activation of Akt signaling in OvCa cells in contact with TGF\u2010\u03b21 stimulated peritoneum, using an <jats:italic>in vivo<\/jats:italic> mice model. Our results suggest that the tumor microenvironment, enhanced by direct cell\u2010to\u2010cell crosstalk between OvCa cells and OCAMs, induces acquisition of platinum\u2010resistance in OvCa cells, which may serve as a novel therapeutic target for prevention of OvCa peritoneal dissemination.<\/jats:p>","DOI":"10.1002\/ijc.32854","type":"journal-article","created":{"date-parts":[[2020,1,6]],"date-time":"2020-01-06T15:16:48Z","timestamp":1578323808000},"page":"2268-2280","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":73,"title":["Ovarian cancer\u2010associated mesothelial cells induce acquired platinum\u2010resistance in peritoneal metastasis <i>via<\/i> the FN1\/Akt signaling pathway"],"prefix":"10.1002","volume":"146","author":[{"given":"Masato","family":"Yoshihara","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0493-1825","authenticated-orcid":false,"given":"Hiroaki","family":"Kajiyama","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Yokoi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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 Japan"},{"name":"Bell Research Center for Reproductive Health and Cancer  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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 Japan"},{"name":"Bell Research Center for Reproductive Health and Cancer  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiko","family":"Yamakita","sequence":"additional","affiliation":[{"name":"Bell Research Center for Reproductive Health and Cancer  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenting","family":"Liu","sequence":"additional","affiliation":[{"name":"Bell Research Center for Reproductive Health and Cancer  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kae","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Bell Research Center, Department of Obstetrics and Gynecology Collaborative Research Nagoya University Graduate School of Medicine  Nagoya Japan"},{"name":"Bell Research Center for Reproductive Health and Cancer  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinori","family":"Moriyama","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Yasui","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiro","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5262-8479","authenticated-orcid":false,"given":"Yusuke","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Division of Molecular and Cellular Medicine National Cancer Center Research Institute  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7415-1854","authenticated-orcid":false,"given":"Carmela","family":"Ricciardelli","sequence":"additional","affiliation":[{"name":"Discipline of Obstetrics and Gynaecology Adelaide Medical School, Robinson Research Institute, University of Adelaide  Adelaide SA Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Nawa","sequence":"additional","affiliation":[{"name":"Bell Research Center, Department of Obstetrics and Gynecology Collaborative Research Nagoya University Graduate School of Medicine  Nagoya Japan"},{"name":"Bell Research Center for Reproductive Health and Cancer  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyosumi","family":"Shibata","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Fujita Health University Bantane Hospital  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumitaka","family":"Kikkawa","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,1,24]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21442"},{"key":"e_1_2_8_3_1","first-page":"1372","article-title":"2016 annual report of the committee on Gynecologic oncology","volume":"70","year":"2018","journal-title":"Acta Obstet Gynaecol Jpn"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21456"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.72.0045"},{"key":"e_1_2_8_6_1","volume-title":"SEER cancer statistics Review, 1975\u20132015","author":"Noone AM","year":"2015"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0000000000000917"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-013-9456-2"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)62146-7"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx441"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2014.02.038"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)13718-X"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(02)00847-1"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2167"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1006\/gyno.1999.5596"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2016.09.005"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4281"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4889"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.23083"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-14-0135"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2018.10.027"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14470"},{"key":"e_1_2_8_23_1","first-page":"193","article-title":"A novel mechanism of neovascularization in peritoneal dissemination via cancer\u2010associated mesothelial cells affected by TGF\u2010\u03b2 derived from ovarian cancer","volume":"39","author":"Fujikake K","year":"2018","journal-title":"Oncol Rep"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11050662"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI33775"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2016.73"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1159\/000063801"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.62.1.65"},{"key":"e_1_2_8_29_1","first-page":"30101","article-title":"Altered proteomic profile in umbilical arterial serum from mothers with schizophrenia","volume":"0920","author":"Moriyama Y","year":"2018","journal-title":"Schizophr Res"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2014.09.006"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-37101-9"},{"key":"e_1_2_8_32_1","unstructured":"National Comprehensive Cancer Network. NCCN Clinical Practice Guideline in Oncology; Ovarian Cancer including Fallopian Tube Cancer and Primary Peritoneal Cancer Version 1.2017. Available at:https:\/\/www.nccn.org\/professionals\/physician_gls\/f_guidelines.asp. (Accessed June 22 2017)."},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10147-016-0985-x"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-10-2289"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-05-0192"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-14-0314"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2013.07.088"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1103799"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)61157-0"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.19.1684"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0020-7292(06)60033-7"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.10.2517"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.23921"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03348-z"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2017.01.015"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa020809"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2006111292"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2014.246"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-12-91"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-08-0196"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI74778"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-16-0320"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2007.11.022"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2018.00130"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-016-2621-6"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-2367"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fijc.32854","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.32854","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ijc.32854","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.32854","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T17:26:53Z","timestamp":1694021213000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.32854"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,24]]},"references-count":55,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2020,4,15]]}},"alternative-id":["10.1002\/ijc.32854"],"URL":"https:\/\/doi.org\/10.1002\/ijc.32854","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,24]]},"assertion":[{"value":"2019-06-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-11-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-01-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}