Ephrin-A2 promotes prostate cancer metastasis by enhancing angiogenesis and promoting EMT.

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 remains elusive. 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, ß-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.

Dry Rolling/Sliding Wear of Bainitic Rail Steels under Different Contact Stresses and Slip Ratios.

This study aims to deeply understand the effect of contact stress and slip ratio on wear performances of bainitic rail steels. The results showed that the wear loss increased as the contact stress and slip ratio increased. Based on the surface damage morphology and microstructural analyses, it revealed that the rolling contact fatigue wear mechanism played a significant role under the low slip ratio, but the dominant wear mechanism transferred to the abrasive wear at the high slip ratio. Meanwhile, the bainitic steel specifically presented worse wear resistance under the abrasive wear mode. Compared with the influence of a slip ratio, the increase in contact stress led to severer plastic flows and contributed to the propagation of cracks. In addition, the contact stress and slip ratio had the opposite effect on the friction coefficient, that is, the friction coefficient of bainitic steels behaved the inverse proportion with the contact stress, but positive proportion with the slip ratio. At last, the increase in slip ratio had more significant effect on the reduction of retained austenite (RA) than the enlargement of contact stress due to the fact that the RA would probably be removed before the martensitic transformation occurred under the abrasive wear mechanism.