Molecular analysis of tumor-vessel interactions during tumor progression

肿瘤进展过程中肿瘤-血管相互作用的分子分析

• 批准号: 22074062
• 负责人: Professor Dr. Hellmut G. Augustin
• 金额: --
• 依托单位: Abteilung Vaskuläre Biologie und Tumorangiogenese
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2006
• 资助国家: 德国
• 起止时间: 2005-12-31 至 2013-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/22074062?language=en
• 关键词: Molecular; analysis; tumor; vessel; interactions

Metastasis results from an intricate bi-directional communication of tumor cells (TC) with cells of the blood and lymphatic vessel wall (EC). Metastatic TC induce angiogenesis, intravasate vessels, travel in the circulation to distant sites, adhere to EC in secondary organs to eventually extravasate and to establish distant metastases. Beyond the induction of angiogenesis, the mechanisms of these multiple TC and EC interactions are poorly understood at the molecular level. We have in previous work characterized the expression, cellular functions and the role during tumor progression and angiogenesis of the EphB4 receptor tyrosine kinase and its corresponding ephrinB2 ligand. These experiments have beyond the established roles of the EphB/ephrinB system for angiogenesis and arteriovenous differentiation provided evidence for a role of EphB receptors and ephrinB ligands in controlling adhesive TC-EC interactions. Based on these findings and additional preliminary data, the present project is aimed at systematically studying in cellular and in vivo experiments adhesive EphB/ephrinB interactions between tumor cells and endothelial cells that control tumor progression and metastasis. The experiments are aimed at shedding light into a novel TC-EC adhesion mechanism. The established platform of relevant cellular and in vivo assays will also be exploited to study other adhesive mechanisms that may be involved in TC metastatic dissemination. Collectively, the experiments will contribute to a better mechanistic understanding of a key step of the metastatic cascade.

转移是肿瘤细胞(TC)与血管和淋巴管壁(EC)细胞复杂的双向通讯的结果。转移的TC诱导血管生成，血管内血管，在循环中移动到远端部位，与次级器官中的EC黏附，最终渗出并建立远端转移。除了诱导血管生成外，这些TC和EC相互作用的机制在分子水平上还知之甚少。我们在以前的工作中已经研究了EphB4受体酪氨酸激酶及其相应的ewitinB2配体的表达、细胞功能以及在肿瘤进展和血管生成中的作用。这些实验已经超越了EphB/ewitinB系统在血管生成和动静脉分化中的既定作用，为EphB受体和eaffinB配体在控制粘附性TC-EC相互作用中的作用提供了证据。基于这些发现和更多的初步数据，本项目的目的是在细胞和体内实验中系统地研究控制肿瘤进展和转移的肿瘤细胞和血管内皮细胞之间的粘附性EphB/ewitinB相互作用。本实验旨在揭示一种新型的TC-EC黏附机制。已建立的相关细胞和体内检测平台也将被用来研究可能涉及TC转移扩散的其他黏附机制。总的来说，这些实验将有助于更好地从机制上理解转移级联的关键步骤。