Regulation of the tumor microenvironment by chronic ß adrenergic activation in the tumor vasculature (C03)

临床数据表明，慢性应激导致癌症进展，-肾上腺素能受体(-2 AR)拮抗剂的使用对疾病结局起到了有益的作用。最近的数据显示，内皮细胞-2AR启动EC促进血管生成，促进前列腺癌的生长和血管生成。我们将分析微血管内皮细胞中持续的2AR激活如何调节血管分泌因子的产生和分泌，以及这些因子如何改变肿瘤微环境以驱动肿瘤进展。已识别的信号中间体如Epac1和转录调节因子-catenin的磷酸化将在相关的体外和体内模型中被验证为潜在的治疗靶点。

Clinical data indicate that chronic stress contributes to cancer progression and that the use of -adrenoceptor (2 AR) antagonists exerts a beneficial effect for disease outcome. Recent data show that endothelial 2AR prime EC for angiogenesis promoting the growth and the vascularization of prostate cancer. We will analyze how persistent 2AR activation in the microvascular endothelium regulates pro-duction and secretion of angiocrine factors and how these factors modify the tumor microenvironment to drive tumor progression. Identified signaling intermediates like Epac1 and the phosphorylation of the transcriptional regulator -catenin will be validated as potential therapeutic targets in relevant in vitro and in vivo models.