Lymphangiogenesis and cancer

肿瘤诱导的淋巴管生成已成为肿瘤细胞进入淋巴管和随后的淋巴结转移形成的重要驱动力。肿瘤产生的血管内皮生长因子C和血管内皮生长因子D激活淋巴管内皮细胞上的VEGFR-3在调节这一过程中起着核心作用。因此，VEGFR-3代表了旨在抑制转移的癌症治疗的一个有希望的靶点。然而，其他促淋巴管生成因子也是由肿瘤产生的，这些也可能在肿瘤诱导的淋巴管生成中起作用。因此，我们建议探索这些前淋巴管生成因子在肿瘤诱导的淋巴管生成和转移中的相对贡献。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细胞的影响，并确定这些作用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治疗只有在不仅抑制淋巴转移而且抑制重要器官转移的情况下才有效。因此，我们还计划对所有从原发肿瘤进入淋巴系统的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，评估它们在重要器官转移形成中的相对贡献。

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.