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CD105 Is Expressed in Ovarian Cancer Precursor Lesions and Is Required for Metastasis to the Ovary

Bai, Shoumei and Zhu, Wanhong and Coffman, Lan and Vlad, Anda and Schwartz, Lauren E. and Elishaev, Esther and Drapkin, Ronny and Buckanovich, Ronald J. (2019) CD105 Is Expressed in Ovarian Cancer Precursor Lesions and Is Required for Metastasis to the Ovary. Cancers, 11 (11). p. 1710. ISSN 2072-6694

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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-β 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(−), 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-β 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.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Bai, Shoumeishb99@pitt.edushb99
Zhu, Wanhong
Coffman, Lanlgc14@pitt.edulgc14
Vlad, Andaanvst12@pitt.eduanvst12
Schwartz, Lauren E.
Elishaev, Estherese9@pitt.eduese9
Drapkin, Ronny
Buckanovich, Ronald J.rjb101@pitt.edurjb101
Centers: Other Centers, Institutes, Offices, or Units > Magee-Women's Research Institute
Date: 2 November 2019
Date Type: Publication
Journal or Publication Title: Cancers
Volume: 11
Number: 11
Publisher: MDPI AG
Page Range: p. 1710
DOI or Unique Handle: 10.3390/cancers11111710
Schools and Programs: School of Medicine > Obstetrics, Gynecology, and Reproductive Sciences
Refereed: Yes
Uncontrolled Keywords: High-grade serous ovarian cancers; hematogenous spread; endoglin (CD105); TGF-β; TRC105; serous tubal intraepithelial carcinoma (STIC)
ISSN: 2072-6694
Official URL:
Funders: National Institutes of Health, Miriam and Sheldon G. Adelson Medical Research Foundation
Article Type: Research Article
Date Deposited: 11 Jun 2021 20:32
Last Modified: 11 Jun 2021 20:32


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