Influence of the EphrinB2-EphB4 system on spinal metastasis formation

本文提出的项目分析器官特异性肿瘤细胞播散，特别关注明显脊柱转移的产生。为此，采用建立的实验动物模型（动脉内肿瘤细胞注射），结合生物发光成像和小动物磁共振成像。利用转基因动物模型（内皮型EphrinB2 KO）和EphB4处理的肿瘤细胞，研究EphrinB2-EphB4通路在脊柱转移发生中的作用。EphrinB2-EphB4改变物质的翻译治疗实验将突出这一信号通路作为治疗脊柱转移的合适靶点的重要性。细胞分析的重点将分析肿瘤细胞-内皮细胞相互作用与EphrinB2-EphB4改变的关系。本研究项目的总体目标是确定EphrinB2-EphB4系统作为脊柱转移的关键调节因子和临床有希望的治疗策略。

The herein presented project analyses organspecific tumor cell dissemination with a special focus on the generation of manifest spinal metastasis. For this purpose an established experimental animal model (intraarteriel tumor cell injection) is used in combination with bioluminescence imaging and smal animal MR imaging. Using a transgenic animal model (endothelial EphrinB2 KO) and EphB4 manipulated tumor cells, the role of the EphrinB2-EphB4 pathway for the generation of spinal metastasis is investigated. Translational therapy experiments with EphrinB2-EphB4 altering substances will highlight the importance of this signalling pathway as a suitable target to treat spinal metastasis. The focus of cellular analysis will analyse tumor cell-endothelia cell interactions in relation to EphrinB2-EphB4 alterations. The overall aim of this research project is to identify the EphrinB2-EphB4 system as a key regulator of spinal metastasis and a clinically promising therapy strategy.