{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T05:16:52Z","timestamp":1773638212682,"version":"3.50.1"},"reference-count":51,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2022,7,11]],"date-time":"2022-07-11T00:00:00Z","timestamp":1657497600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004376","name":"Terry Fox Research Institute","doi-asserted-by":"publisher","award":["I1043"],"award-info":[{"award-number":["I1043"]}],"id":[{"id":"10.13039\/501100004376","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004376","name":"Terry Fox Research Institute","doi-asserted-by":"publisher","award":["BT\/PR27126\/MED\/30\/1943\/2017"],"award-info":[{"award-number":["BT\/PR27126\/MED\/30\/1943\/2017"]}],"id":[{"id":"10.13039\/501100004376","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Government of India","doi-asserted-by":"publisher","award":["I1043"],"award-info":[{"award-number":["I1043"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Government of India","doi-asserted-by":"publisher","award":["BT\/PR27126\/MED\/30\/1943\/2017"],"award-info":[{"award-number":["BT\/PR27126\/MED\/30\/1943\/2017"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010489","name":"ACTREC-TMC","doi-asserted-by":"crossref","award":["I1043"],"award-info":[{"award-number":["I1043"]}],"id":[{"id":"10.13039\/501100010489","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100010489","name":"ACTREC-TMC","doi-asserted-by":"crossref","award":["BT\/PR27126\/MED\/30\/1943\/2017"],"award-info":[{"award-number":["BT\/PR27126\/MED\/30\/1943\/2017"]}],"id":[{"id":"10.13039\/501100010489","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Cancers"],"abstract":"<jats:p>An active fluidic microenvironment governs peritoneal metastasis in epithelial ovarian cancer (EOC), but its critical functional\/molecular cues are not fully understood. Utilizing co-culture models of NIH3T3 cells (differentially overexpressing Jagged1) and SKOV3 cells expressing a Notch3 luciferase reporter-sensor (SNFT), we showed that incremental expression of Jagged1 led to proportional Notch3 activation in SNFT. With no basal luciferase activity, this system efficiently recorded dose-dependent Notch3 activation by rh-Jag1 peptide and the non-appearance of such induction in co-culture with NIH3T3\u0394jag1 cells indicates its sensitivity and specificity. Similar Notch3 modulation was shown for the first time in co-cultures with HGSOC patients\u2019 ascites-derived cancer-associated fibroblasts and Jagged1-expressing EOC cell lines. NIH3T3J1-A and OVCAR3 co-cultured SNFT cells showed maximum proliferation, invasion, and cisplatin resistance among all the heterotypic\/homotypic cellular partners. VEGFA and CDKN1A are the two most upregulated genes identified across co-cultures by the gene profiler array. Co-culture induced VEGFA secretion from SNFT cells which also reduced cancer stem cell differentiation in platinum-resistant A2780 cells. rh-Jag1-peptide promoted enhanced nuclear-cytoplasmic p21 expression. Additionally, metastatic HGSOC tumors had higher VEGFA than corresponding primary tumors. This study thus demonstrates the tumoral and non-tumoral cell-mediated differential Notch3 activation imparting its tumorigenic effects through two critical molecular regulators, VEGFA and p21, during EOC progression.<\/jats:p>","DOI":"10.3390\/cancers14143365","type":"journal-article","created":{"date-parts":[[2022,7,11]],"date-time":"2022-07-11T21:57:53Z","timestamp":1657576673000},"page":"3365","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Homo and Heterotypic Cellular Cross-Talk in Epithelial Ovarian Cancer Impart Pro-Tumorigenic Properties through Differential Activation of the Notch3 Pathway"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6435-2994","authenticated-orcid":false,"given":"Souvik","family":"Mukherjee","sequence":"first","affiliation":[{"name":"Imaging Cell Signaling and Therapeutics Lab, Advanced Centre for Training Research and Education in Cancer, Navi Mumbai 410210, India"},{"name":"Homi Bhabha National Institute, BARC Training School Complex, Anushaktinagar, Mumbai 400094, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asmita","family":"Sakpal","sequence":"additional","affiliation":[{"name":"Imaging Cell Signaling and Therapeutics Lab, Advanced Centre for Training Research and Education in Cancer, Navi Mumbai 410210, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megha","family":"Mehrotra","sequence":"additional","affiliation":[{"name":"Imaging Cell Signaling and Therapeutics Lab, Advanced Centre for Training Research and Education in Cancer, Navi Mumbai 410210, India"},{"name":"Homi Bhabha National Institute, BARC Training School Complex, Anushaktinagar, Mumbai 400094, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pratham","family":"Phadte","sequence":"additional","affiliation":[{"name":"Imaging Cell Signaling and Therapeutics Lab, Advanced Centre for Training Research and Education in Cancer, Navi Mumbai 410210, India"},{"name":"Homi Bhabha National Institute, BARC Training School Complex, Anushaktinagar, Mumbai 400094, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3509-4794","authenticated-orcid":false,"given":"Bharat","family":"Rekhi","sequence":"additional","affiliation":[{"name":"Homi Bhabha National Institute, BARC Training School Complex, Anushaktinagar, Mumbai 400094, India"},{"name":"Tata Memorial Hospital, Dr. E Borges Road, Parel, Mumbai 400012, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pritha","family":"Ray","sequence":"additional","affiliation":[{"name":"Imaging Cell Signaling and Therapeutics Lab, Advanced Centre for Training Research and Education in Cancer, Navi Mumbai 410210, India"},{"name":"Homi Bhabha National Institute, BARC Training School Complex, Anushaktinagar, Mumbai 400094, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.trecan.2016.12.005","article-title":"Tumor-Host Cell Interactions in Ovarian Cancer: Pathways to Therapy Failure","volume":"3","author":"Reinartz","year":"2017","journal-title":"Trends Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/s41576-020-00292-x","article-title":"Deciphering cell-cell interactions and communication from gene expression","volume":"22","author":"Armingol","year":"2021","journal-title":"Nat. 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