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Endoglin is necessary for angiogenesis in human ovarian carcinoma-derived primary endothelial cells.

ABSTRACT: Endoglin (CD105, END) is upregulated in proliferating endothelial cells, suggesting potential therapeutic properties. However, it is not clear whether endoglin mediates an enhanced proliferative rate or may be upregulated as part of a negative feedback loop. To gain insights into context-dependent and cell type-dependent regulatory effects of endoglin, we studied its role properties in human ovarian carcinoma-derived endothelial cells (ODMECs). We isolated and cultured primary ODMECs from epithelial ovarian carcinoma tissue. ODMECs had higher expression of endoglin and VEGFR-2, and also exhibited enhanced spontaneous formation of vessel-like structures in vitro. Transfection of siRNA targeting endoglin in ODMECs cells resulted in the reduction of the proliferation and tube formation. These results indicate that a subset of ODMECs display abnormal angiogenic properties and this phenotype was blocked by decreasing endoglin levels, suggesting endoglin is essential for stimulating angiogenesis, and targeting it may be an attractive approach to anti-angiogenesis therapy for ovarian carcinoma.

SUBMITTER: Xu Y

PROVIDER: S-EPMC3926891 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Endoglin is necessary for angiogenesis in human ovarian carcinoma-derived primary endothelial cells.

Xu Yan Y Wang Dan D Zhao Li-Mei LM Zhao Xi-Long XL Shen Jun-Jie JJ Xie Yao Y Cao Li-Li LL Chen Zhen-Bo ZB Luo Yan-Mei YM Bao Bi-Hui BH Liang Zhi-Qing ZQ

Cancer biology & therapy 20130805 10

Endoglin (CD105, END) is upregulated in proliferating endothelial cells, suggesting potential therapeutic properties. However, it is not clear whether endoglin mediates an enhanced proliferative rate or may be upregulated as part of a negative feedback loop. To gain insights into context-dependent and cell type-dependent regulatory effects of endoglin, we studied its role properties in human ovarian carcinoma-derived endothelial cells (ODMECs). We isolated and cultured primary ODMECs from epithe ...[more]

PMID: 23917399

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Project description:Regulator of G?protein signaling 5 (RGS5), a tissue?speci?c signal?regulating molecule, plays a key role in the development of the vasculature. It was recently found that RGS5 is abundantly expressed in epithelial ovarian cancer (EOC) compared with the normal ovaries. However, the distribution of RGS5 in EOC and its signi?cance require further investigation. The aim of the present study was to investigate the expression of RGS5 in EOC, as well as its association with cancer differentiation, metastasis and clinicopathological parameters. Immunohistochemistry (IHC), western blotting, RT?PCR, wound?healing, cell proliferation and flow cytometric assays were the methods used in the present study. RGS5 was highly expressed in the cytoplasm of ovarian carcinoma cells and in microvascular structures. The expression of RGS5 in EOC was negatively associated with peritoneal metastasis (P=0.004), but it was not found to be associated with age, tumor size, clinical stage or lymph node metastasis (P>0.05). EOC patients with high RGS5 expression had a prolonged progression?free survival (72.34±8.41 vs. 43.56±5.41 months, P<0.001). High expression of RGS5 was correlated with significantly lower microvascular density (MVD) as indicated by the expression of CD34, whereas the opposite was observed in tissues with low RGS5 expression (P<0.05). Hypoxia increased RGS5 expression in ovarian carcinoma?derived endothelial cells (ODMECs), whereas the proliferative capacity of ODMECs exhibited a significant increase following RNAi?mediated reduction of RGS5 expression. These data indicated that RGS5 plays a key role in angiogenesis in ovarian carcinoma. In addition, RGS5 downregulated the expression of the downstream proteins CDC25A, CDK2 and cyclin E, which are mediated by the mitogen?activated protein kinase/extracellular signal?regulated kinase pathway, causing ODMEC arrest in the G1 phase of the cell cycle under hypoxic conditions. Collectively, our data indicated that RGS5 is crucial for the occurrence and development of ovarian cancer, and that RGS5 and its signaling pathway may serve as anti?angiogenesis targets for the treatment of ovarian cancer.

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Dataset Information

Endoglin is necessary for angiogenesis in human ovarian carcinoma-derived primary endothelial cells.

Publications

Endoglin is necessary for angiogenesis in human ovarian carcinoma-derived primary endothelial cells.

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