Inhibition of VEGF-dependent multistage carcinogenesis by soluble EphA receptors.

摘要: Elevated expression of Eph receptors has long been correlated with the growth solid tumors. However, functional role this family receptor tyrosine kinases in carcinogenesis and tumor angiogenesis not well characterized. Here we report that soluble EphA inhibit progression vivo RIP-Tag transgenic model vascular endothelial factor (VEGF)-dependent multistage pancreatic islet cell carcinoma. Soluble delivered either by a transgene or an osmotic minipump inhibited formation angiogenic islet, premalignant lesion, reduced volume EphA2-Fc EphA3-Fc treatment resulted decreased but increased apoptosis vivo. In addition, VEGF βTC cell-conditioned medium-induced migration vitro VEGF-induced cornea A dominant negative EphA2 mutant inhibited—whereas gain-of-function enhanced—tumor cell-induced migration, suggesting activation is required for cell-endothelial interaction. These data provide evidence class regulation VEGF-dependent angiogenesis, signaling pathway may represent attractive novel target antiangiogenic therapy cancer.