Lymphangiogenesis and cancer

淋巴管生成与癌症

• 批准号: 22033752
• 负责人: Professor Dr. Jonathan Paul Sleeman
• 金额: --
• 依托单位: European Center for Angioscience (ECAS)
• 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/22033752?language=en
• 关键词: Lymphangiogenesis; cancer

Tumor-induced lymphangiogenesis has emerged as an important driving force behind the entry of tumor cells into the lymphatics and subsequent metastasis formation in lymph nodes. VEGFR-3 activation on lymphatic endothelial cells in response to VEGF-C and VEGF-D produced by tumors plays a central role in regulating this process. VEGFR-3 therefore represents a promising target for cancer therapies aimed at suppressing metastasis. However, other pro-lymphangiogenic factors are also produced by tumors, and these may also make a contribution to tumor-induced lymphangiogeneis. We therefore propose to explore the relative contribution of these prolymphangiogenic factors to tumor-induced lymphangiogenesis and metastasis. We also plan to investigate the effects of tumor-produced degradation products of hyaluronate on the lymphatic endothelium, and to determine whether these contribute to tumor-induced lymphangiogenesis and metastasis. Therapies directed against tumor-induced lymphangiogenesis will only be effective if they inhibit not only metastasis to lymph nodes but also to vital organs. Thus we also plan to genetically mark all tumor cells that enter the lymphatic system from the primary tumor, then to assess their relative contribution to metastasis formation in vital organs in comparison to tumor cells that have only circulated in the blood.

肿瘤诱导的淋巴管生成已成为肿瘤细胞进入淋巴管并随后在淋巴结中形成转移的重要驱动力。淋巴内皮细胞响应肿瘤产生的 VEGF-C 和 VEGF-D 而激活 VEGFR-3，在调节这一过程中发挥着核心作用。因此，VEGFR-3 代表了旨在抑制转移的癌症治疗的一个有前景的靶点。然而，肿瘤也产生其他促淋巴管生成因子，这些因子也可能对肿瘤诱导的淋巴管生成做出贡献。因此，我们建议探索这些前淋巴管生成因子对肿瘤诱导的淋巴管生成和转移的相对贡献。我们还计划研究肿瘤产生的透明质酸降解产物对淋巴管内皮的影响，并确定它们是否有助于肿瘤诱导的淋巴管生成和转移。针对肿瘤诱导的淋巴管生成的疗法只有在不仅抑制淋巴结转移而且抑制重要器官转移时才有效。因此，我们还计划对从原发肿瘤进入淋巴系统的所有肿瘤细胞进行基因标记，然后与仅在血液中循环的肿瘤细胞相比，评估它们对重要器官转移形成的相对贡献。