التفاصيل البيبلوغرافية
| العنوان: |
CD105 Is Expressed in Ovarian Cancer Precursor Lesions and Is Required for Metastasis to the Ovary |
| المؤلفون: |
Shoumei Bai, Wanhong Zhu, Lan Coffman, Anda Vlad, Lauren E. Schwartz, Esther Elishaev, Ronny Drapkin, Ronald J. Buckanovich |
| المصدر: |
Cancers; Volume 11; Issue 11; Pages: 1710 |
| بيانات النشر: |
Multidisciplinary Digital Publishing Institute |
| سنة النشر: |
2019 |
| المجموعة: |
MDPI Open Access Publishing |
| مصطلحات موضوعية: |
High-grade serous ovarian cancers, hematogenous spread, endoglin (CD105), TGF-β, TRC105, serous tubal intraepithelial carcinoma (STIC) |
| الوصف: |
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. |
| نوع الوثيقة: |
text |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| Relation: |
https://dx.doi.org/10.3390/cancers11111710 |
| DOI: |
10.3390/cancers11111710 |
| الاتاحة: |
https://doi.org/10.3390/cancers11111710 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: |
edsbas.3DA3038B |
| قاعدة البيانات: |
BASE |