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

通过肿瘤脉管系统中的慢性肾上腺素能激活调节肿瘤微环境 (C03)

• 批准号: 418412983
• 金额: --
• 依托单位: Abteilung Experimentelle Pharmakologie
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/418412983?language=en
• 关键词: Regulation; tumor; microenvironment; chronic; adrenergic

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.

临床数据表明，慢性应激有助于癌症进展，并且使用β-肾上腺素受体（β 2 AR）拮抗剂对疾病结果发挥有益作用。最近的数据表明，内皮细胞的β 2 AR总理EC血管生成促进前列腺癌的生长和血管化。我们将分析微血管内皮细胞中持续的β 2 AR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。已鉴定的信号传导中间体如Epac 1和转录调节因子β-连环蛋白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。