Next Article in Journal
STAT3 Dysregulation in Mature T and NK Cell Lymphomas
Previous Article in Journal
Quantitative, Multi-institutional Evaluation of MR Thermometry Accuracy for Deep-Pelvic MR-Hyperthermia Systems Operating in Multi-vendor MR-systems Using a New Anthropomorphic Phantom
Article

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

1
Magee-Womens Research Institute, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA 15213, USA
2
Division of Hematology-Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA
3
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
4
Penn Ovarian Cancer Research Center, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
5
Hillman Cancer Center, Division of Hematology Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA 15232, USA
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(11), 1710; https://doi.org/10.3390/cancers11111710
Received: 11 October 2019 / Revised: 28 October 2019 / Accepted: 29 October 2019 / Published: 2 November 2019
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. View Full-Text
Keywords: High-grade serous ovarian cancers; hematogenous spread; endoglin (CD105); TGF-β; TRC105; serous tubal intraepithelial carcinoma (STIC) High-grade serous ovarian cancers; hematogenous spread; endoglin (CD105); TGF-β; TRC105; serous tubal intraepithelial carcinoma (STIC)
Show Figures

Figure 1

MDPI and ACS Style

Bai, S.; Zhu, W.; Coffman, L.; Vlad, A.; Schwartz, L.E.; Elishaev, E.; Drapkin, R.; Buckanovich, R.J. CD105 Is Expressed in Ovarian Cancer Precursor Lesions and Is Required for Metastasis to the Ovary. Cancers 2019, 11, 1710. https://doi.org/10.3390/cancers11111710

AMA Style

Bai S, Zhu W, Coffman L, Vlad A, Schwartz LE, Elishaev E, Drapkin R, Buckanovich RJ. CD105 Is Expressed in Ovarian Cancer Precursor Lesions and Is Required for Metastasis to the Ovary. Cancers. 2019; 11(11):1710. https://doi.org/10.3390/cancers11111710

Chicago/Turabian Style

Bai, Shoumei, Wanhong Zhu, Lan Coffman, Anda Vlad, Lauren E. Schwartz, Esther Elishaev, Ronny Drapkin, and Ronald J. Buckanovich. 2019. "CD105 Is Expressed in Ovarian Cancer Precursor Lesions and Is Required for Metastasis to the Ovary" Cancers 11, no. 11: 1710. https://doi.org/10.3390/cancers11111710

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop