1. Ephrin-A2 promotes prostate cancer metastasis by enhancing angiogenesis and promoting EMT
- Author
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Miaomiao Zhang, Shibao Li, Ping Ma, Haoliang Zhang, Yao Zhao, Lubing Shi, Jiwei Wang, and Chenchen Cai
- Subjects
Male ,0301 basic medicine ,Cancer Research ,Epithelial-Mesenchymal Transition ,animal structures ,Angiogenesis ,Mice, Nude ,Apoptosis ,Metastasis ,Mice ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Cell Movement ,Biomarkers, Tumor ,Tumor Cells, Cultured ,medicine ,Animals ,Humans ,Gene silencing ,Neoplasm Metastasis ,Cell Proliferation ,Mice, Inbred BALB C ,Neovascularization, Pathologic ,business.industry ,Erythropoietin-producing hepatocellular (Eph) receptor ,Ephrin-A2 ,Prostatic Neoplasms ,Cell migration ,General Medicine ,medicine.disease ,Xenograft Model Antitumor Assays ,Primary tumor ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,embryonic structures ,Cancer research ,Ectopic expression ,sense organs ,business - Abstract
Background Ephrin-A2, a member of the Eph receptor subgroup, is used in diagnosing and determining the prognosis of prostate cancer. However, the role of ephrin-A2 in prostate cancer is still unclear. Methods We established stable clones overexpressing or silencing ephrin-A2 from prostate cancer cells. Then, CCK-8 was used in analyzing the proliferation ability of cells. CD31 staining was used in evaluating angiogenesis. Migration and invasion assay were conducted in vivo and in vitro. The expression of EMT-related markers was evaluated in prostate cancer cells through Western blotting. Results We revealed that the ectopic expression of ephrin-A2 in prostate cancer cells facilitated cell migration and invasion in vitro and promoted tumor metastasis and angiogenesis in vivo and that the silencing of ephrin-A2 completely reversed this effect. Although ephrin-A2 did not affect tumor cell proliferation in vitro, ephrin-A2 significantly promoted primary tumor growth in vivo. Furthermore, to determine the biological function of ephrin-A2, we assayed the expression of EMT-related markers in stable established cell lines. Results showed that the overexpression of ephrin-A2 in prostate cancer cells down-regulated the expression of epithelial markers (ZO-1, E-cadherin, and claudin-1) and up-regulated the expression of mesenchymal markers (N-cadherin, β-catenin, vimentin, Slug, and Snail), but the knocking out of ephrin-A2 opposed the effects on the expression of EMT markers. Conclusions These findings indicate that ephrin-A2 promotes prostate cancer metastasis by enhancing angiogenesis and promoting EMT and may be a potentially therapeutic target in metastatic prostate cancer.
- Published
- 2021