{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:21:48Z","timestamp":1791390108857,"version":"4.3.3"},"reference-count":44,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,13]],"date-time":"2022-01-13T00:00:00Z","timestamp":1642032000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ricerca Corrente Ministero Salute 2021 to MFDR","award":["."],"award-info":[{"award-number":["."]}]},{"name":"FPRC 5xmille Ministero Salute 2015 &quot;Strategy&quot; to MFDR","award":["."],"award-info":[{"award-number":["."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Peritoneal metastases are the leading cause of morbidity and mortality in ovarian cancer. Cancer cells float in peritoneal fluid, named ascites, together with a definitely higher number of non neo-neoplastic cells, as single cells or multicellular aggregates. The aim of this work is to uncover the features that make these aggregates the metastasizing units. Immunofluorescence revealed that aggregates are made almost exclusively of ovarian cancer cells expressing the specific nuclear PAX8 protein. The same cells expressed epithelial and mesenchymal markers, such as EPCAM and \u03b1SMA, respectively. Expression of fibronectin further supported a hybrid epithelia-mesenchymal phenotype, that is maintained when aggregates are cultivated and proliferate. Hematopoietic cells as well as macrophages are negligible in the aggregates, while abundant in the ascitic fluid confirming their prominent role in establishing an eco-system necessary for the survival of ovarian cancer cells. Using ovarian cancer cell lines, we show that cells forming 3D structures neo-expressed thoroughly fibronectin and \u03b1SMA. Functional assays showed that \u03b1SMA and fibronectin are necessary for the compaction and survival of 3D structures. Altogether these data show that metastasizing units display a hybrid phenotype that allows maintenance of the 3D structures and the plasticity necessary for implant and seeding into peritoneal lining.<\/jats:p>","DOI":"10.3390\/ijms23020833","type":"journal-article","created":{"date-parts":[[2022,1,13]],"date-time":"2022-01-13T10:57:37Z","timestamp":1642071457000},"page":"833","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Ovarian Cancer Cells in Ascites Form Aggregates That Display a Hybrid Epithelial-Mesenchymal Phenotype and Allows Survival and Proliferation of Metastasizing Cells"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9043-9014","authenticated-orcid":false,"given":"Sonia","family":"Capellero","sequence":"first","affiliation":[{"name":"Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy"},{"name":"Department of Oncology, University of Torino, 10129 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7152-0930","authenticated-orcid":false,"given":"Jessica","family":"Erriquez","sequence":"additional","affiliation":[{"name":"Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3583-290X","authenticated-orcid":false,"given":"Chiara","family":"Battistini","sequence":"additional","affiliation":[{"name":"Unit of Gynaecological Oncology Research, European Institute of Oncology, IRCCS, 20100 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Porporato","sequence":"additional","affiliation":[{"name":"Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Scotto","sequence":"additional","affiliation":[{"name":"Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy"},{"name":"Department of Oncology, University of Torino, 10129 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8398-7557","authenticated-orcid":false,"given":"Fulvio","family":"Borella","sequence":"additional","affiliation":[{"name":"Gynecology and Obstetrics 1, Department of Surgical Sciences, City of Health and Science, University of Turin, 10100 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria F.","family":"Di Renzo","sequence":"additional","affiliation":[{"name":"Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy"},{"name":"Department of Oncology, University of Torino, 10129 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5444-6305","authenticated-orcid":false,"given":"Giorgio","family":"Valabrega","sequence":"additional","affiliation":[{"name":"Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy"},{"name":"Department of Oncology, University of Torino, 10129 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Olivero","sequence":"additional","affiliation":[{"name":"Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy"},{"name":"Department of Oncology, University of Torino, 10129 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1038\/nrc4019","article-title":"Rethinking ovarian cancer II: Reducing mortality from high-grade serous ovarian cancer","volume":"15","author":"Bowtell","year":"2015","journal-title":"Nat. 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