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Here, we describe the aggressive nature of HGSOC ascitic tumor cells (ATCs) characterized by integrin \u03b15high (ITGA5high) ATCs, which are prone to forming heterotypic spheroids with fibroblasts. We term these aggregates as metastatic units (MUs) in HGSOC for their advantageous metastatic capacity and active involvement in early peritoneal dissemination. Intriguingly, fibroblasts inside MUs support ATC survival and guide their peritoneal invasion before becoming essential components of the tumor stroma in newly formed metastases. Cancer-associated fibroblasts (CAFs) recruit ITGA5high ATCs to form MUs, which further sustain ATC ITGA5 expression by EGF secretion. Notably, LGSOC is largely devoid of CAFs and the resultant MUs, which might explain its metastatic delay. These findings identify a specialized MU architecture that amplifies the tumor\u2013stroma interaction and promotes transcoelomic metastasis in HGSOC, providing the basis for stromal fibroblast-oriented interventions in hampering OC peritoneal propagation.<\/jats:p>","DOI":"10.1084\/jem.20180765","type":"journal-article","created":{"date-parts":[[2019,2,1]],"date-time":"2019-02-01T15:06:26Z","timestamp":1549033586000},"page":"688-703","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":212,"title":["Heterotypic CAF-tumor spheroids promote early peritoneal metastasis of ovarian cancer"],"prefix":"10.1084","volume":"216","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9448-3423","authenticated-orcid":true,"given":"Qinglei","family":"Gao","sequence":"first","affiliation":[{"name":"Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science 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