The chemokine crosstalk at the 'tumor-vessel interface'

“肿瘤-血管界面”处的趋化因子串扰

• 批准号: 22053238
• 负责人: Professor Dr. Bernhard Homey
• 金额: --
• 依托单位: Hautklinik
• 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 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/22053238?language=en
• 关键词: chemokine; crosstalk; tumor; vessel; interface

During tumor progression, malignant cells interact with stromal cells and modulate both hemangio- as well as lymphangiogenesis. Subsequently, intravasation of tumor cells starts a cascade finally leading to survival-limiting metastasis formation. These processes suggest bidirectional communication pathways guiding sprouting microvessels to tumors and instructing tumor cells to intravasate. To date, the underlying chemoattractive signals remain largely unknown. In the present project, we will investigate whether tumor cell-derived chemokines organize lymphangiogenesis and chemokines produced by lymphatic endothelial cells enable tumor cells to invade into lymphatic vessels initiating metastatic dissemination. To address these questions, we will take advantage of the scientific expertise within the SPP1190 consortium and use state of the art imaging tools, tumor models as well unique models of in vitro and in vivo lymphangiogenesis. Within the consortium, we will provide expertise on chemokines and their receptors, qPCR analysis of all known human and mouse chemokines/receptors, human immortalized blood and lymphatic microvascular endothelial cells, CCR6-, CCR8-, CCR9-deficient mice, neutralizing anti-chemokine and antichemokine receptor antibodies as well as chemokine receptor antagonists.

在肿瘤进展过程中，恶性细胞与基质细胞相互作用并调节血管生成和淋巴管生成。随后，肿瘤细胞的内渗启动级联反应，最终导致限制生存的转移形成。这些过程表明双向通讯途径将萌发的微血管引导至肿瘤并指示肿瘤细胞渗入。迄今为止，潜在的化学吸引信号仍然很大程度上未知。在本项目中，我们将研究肿瘤细胞衍生的趋化因子是否组织淋巴管生成，以及淋巴管内皮细胞产生的趋化因子是否使肿瘤细胞能够侵入淋巴管从而引发转移性播散。为了解决这些问题，我们将利用 SPP1190 联盟的科学专业知识，并使用最先进的成像工具、肿瘤模型以及独特的体外和体内淋巴管生成模型。在联盟内，我们将提供趋化因子及其受体的专业知识、所有已知人类和小鼠趋化因子/受体的 qPCR 分析、人类永生化血液和淋巴微血管内皮细胞、CCR6、CCR8、CCR9 缺陷小鼠、中和抗趋化因子和抗趋化因子受体抗体以及趋化因子受体拮抗剂。