{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T13:34:24Z","timestamp":1787837664863,"version":"build-2784847793"},"reference-count":70,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T00:00:00Z","timestamp":1668556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008982","name":"Qatar National Research Fund","doi-asserted-by":"publisher","award":["NPRP 8-1898-3-392"],"award-info":[{"award-number":["NPRP 8-1898-3-392"]}],"id":[{"id":"10.13039\/100008982","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008982","name":"Qatar National Research Fund","doi-asserted-by":"publisher","award":["NPRP 09-1174-3-291"],"award-info":[{"award-number":["NPRP 09-1174-3-291"]}],"id":[{"id":"10.13039\/100008982","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008982","name":"Qatar National Research Fund","doi-asserted-by":"publisher","award":["NPRP 4-640-1-096"],"award-info":[{"award-number":["NPRP 4-640-1-096"]}],"id":[{"id":"10.13039\/100008982","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Ovarian cancer (OC) is a heterogeneous disease characterized by its late diagnosis (FIGO stages III and IV) and the importance of abdominal metastases often observed at diagnosis. Detached ovarian cancer cells (OCCs) float in ascites and form multicellular spheroids. Here, we developed endothelial cell (EC)-based 3D spheroids to better represent in vivo conditions. When co-cultured in 3D conditions, ECs and OCCs formed organized tumor angiospheres with a core of ECs surrounded by proliferating OCCs. We established that Akt and Notch3\/Jagged1 pathways played a role in angiosphere formation and peritoneum invasion. In patients\u2019 ascites we found angiosphere-like structures and demonstrated in patients\u2019 specimens that tumoral EC displayed Akt activation, which supports the importance of Akt activation in ECs in OC. Additionally, we demonstrated the importance of FGF2, Pentraxin 3 (PTX3), PD-ECGF and TIMP-1 in angiosphere organization. Finally, we confirmed the role of Notch3\/Jagged1 in OCC\u2013EC crosstalk relating to OCC proliferation and during peritoneal invasion. Our results support the use of multicellular spheroids to better model tumoral and stromal interaction. Such models could help decipher the complex pathways playing critical roles in metastasis spread and predict tumor response to chemotherapy or anti-angiogenic treatment.<\/jats:p>","DOI":"10.3390\/ijms232214173","type":"journal-article","created":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T03:05:21Z","timestamp":1668654321000},"page":"14173","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Akt-Activated Endothelium Increases Cancer Cell Proliferation and Resistance to Treatment in Ovarian Cancer Cell Organoids"],"prefix":"10.3390","volume":"23","author":[{"given":"Jessica","family":"Hoarau-V\u00e9chot","sequence":"first","affiliation":[{"name":"Department of Genetic Medicine and Obstetrics and Gynecology, Genetic Intelligence Laboratory, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha P.O. Box 24144, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgane","family":"Blot-Dupin","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de M\u00e9decine de Cr\u00e9teil UPEC\u2014Paris XII, Service de Gyn\u00e9cologie-Obst\u00e9trique et M\u00e9decine de la Reproduction, Centre Hospitalier Intercommunal de Cr\u00e9teil, 40 Avenue de Verdun, 94000 Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9626-7428","authenticated-orcid":false,"given":"L\u00e9a","family":"Pauly","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de M\u00e9decine de Cr\u00e9teil UPEC\u2014Paris XII, Service de Gyn\u00e9cologie-Obst\u00e9trique et M\u00e9decine de la Reproduction, Centre Hospitalier Intercommunal de Cr\u00e9teil, 40 Avenue de Verdun, 94000 Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9149-1663","authenticated-orcid":false,"given":"Cyril","family":"Touboul","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), Centre National de la Recherche Scientifique (CNRS), UMR_S 938, Centre de Recherche Saint-Antoine, Team Cancer Biology and Therapeutics, Institut Universitaire de Canc\u00e9rologie, Sorbonne Universit\u00e9, 75012 Paris, France"},{"name":"Department of Obstetrics and Gynecology, H\u00f4pital Tenon, Assistance Publique Des H\u00f4pitaux de Paris, GRC-6 UPMC, Universit\u00e9 Pierre et Marie Curie, 75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahin","family":"Rafii","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine, Weill Cornell Medicine, New York, NY 10021, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arash","family":"Rafii","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine and Obstetrics and Gynecology, Genetic Intelligence Laboratory, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha P.O. Box 24144, Qatar"},{"name":"Department of Genetic Medicine, Weill Cornell Medicine, New York, NY 10021, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Pasquier","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine and Obstetrics and Gynecology, Genetic Intelligence Laboratory, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha P.O. Box 24144, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"280","DOI":"10.3322\/caac.21559","article-title":"Epithelial ovarian cancer: Evolution of management in the era of precision medicine","volume":"69","author":"Lheureux","year":"2019","journal-title":"CA Cancer J. 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