{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:38:45Z","timestamp":1791380325795,"version":"4.3.3"},"reference-count":50,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2019,11,2]],"date-time":"2019-11-02T00:00:00Z","timestamp":1572652800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5R01CA211913"],"award-info":[{"award-number":["5R01CA211913"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P50CA228992"],"award-info":[{"award-number":["P50CA228992"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Most high-grade serous ovarian cancers (HGSCs) initiate from the fallopian tube epithelium and then metastasize to the ovary and throughout the abdomen. Genomic analyses suggest that most HGSCs seed the ovary prior to abdominal dissemination. Similarly, animal models support a critical role for the ovary in driving abdominal dissemination. Thus, HGSC cell recruitment to the ovary appears to be a critical component of HGSC cell metastasis. We sought to identify factors driving HGSC recruitment to the ovary. We identified CD105 (endoglin, or ENG, a TGF-\u03b2 receptor family member) as a mediator of HGSC cell ovarian recruitment. We found that CD105 was expressed on both serous tubal intraepithelial carcinoma (STIC) cells (STICs-HGSC precursors in the fallopian tube epithelium) and HGSC cells. Using data from The Cancer Genome Atlas (TCGA) and the Cancer Cell Line Encyclopedia (CCLE), we showed that high CD105 expression by HGSC cells correlated with a metastatic signature. Furthermore, intravenous injection of CD105(+) HGSC tumor cells, but not CD105(\u2212), resulted in ovarian-specific metastasis and abdominal dissemination of disease. CD105 knockdown or blockade with a clinically relevant CD105-neutralizing mAb (TRC105), inhibited HGSC metastasis, reduced ascites, and impeded growth of abdominal tumor nodules, thereby improving overall survival in animal models of ovarian cancer. CD105 knockdown was associated with a reduction in TGF-\u03b2 signaling. Together, our data support CD105 as a critical mediator of ovarian cancer spread to the ovary and implicate it as a potential therapeutic target.<\/jats:p>","DOI":"10.3390\/cancers11111710","type":"journal-article","created":{"date-parts":[[2019,11,4]],"date-time":"2019-11-04T04:13:08Z","timestamp":1572840788000},"page":"1710","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["CD105 Is Expressed in Ovarian Cancer Precursor Lesions and Is Required for Metastasis to the Ovary"],"prefix":"10.3390","volume":"11","author":[{"given":"Shoumei","family":"Bai","sequence":"first","affiliation":[{"name":"Magee-Womens Research Institute, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanhong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Coffman","sequence":"additional","affiliation":[{"name":"Magee-Womens Research Institute, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anda","family":"Vlad","sequence":"additional","affiliation":[{"name":"Magee-Womens Research Institute, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren E.","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Elishaev","sequence":"additional","affiliation":[{"name":"Magee-Womens Research Institute, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6912-6977","authenticated-orcid":false,"given":"Ronny","family":"Drapkin","sequence":"additional","affiliation":[{"name":"Penn Ovarian Cancer Research Center, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald J.","family":"Buckanovich","sequence":"additional","affiliation":[{"name":"Magee-Womens Research Institute, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA 15213, USA"},{"name":"Hillman Cancer Center, Division of Hematology Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA 15232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,2]]},"reference":[{"key":"ref_1","first-page":"3584","article-title":"Mechanisms of human tumor metastasis studied in patients with peritoneovenous shunts","volume":"44","author":"Tarin","year":"1984","journal-title":"Cancer Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/s13277-015-4299-9","article-title":"Circulating tumor cells as trigger to hematogenous spreads and potential biomarkers to predict the prognosis in ovarian cancer","volume":"37","author":"Gasparri","year":"2016","journal-title":"Tumor Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"746","DOI":"10.18632\/genesandcancer.162","article-title":"ERBB signaling in CTCs of ovarian cancer and glioblastoma","volume":"8","author":"Geethadevi","year":"2017","journal-title":"Genes Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/j.ygyno.2014.03.016","article-title":"Circulating and disseminated tumor cells in ovarian cancer: A systematic review","volume":"133","author":"Olmos","year":"2014","journal-title":"Gynecol. 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