文章：

淋巴管生成和肿瘤转移

Lymphangiogenesis and cancer metastasis

原文发布日期：2002-08-01

DOI: 10.1038/nrc863

类型: Review Article

开放获取: 否

要点：

1. Tumour metastasis to regional lymph nodes is a crucial step in the progression of cancer. Detection of tumour cells in the lymph nodes is an indication of the spread of the tumour, and is used clinically as a prognostic tool and a guide to therapy. However, the molecular mechanisms that control the spread of cancer to the lymph nodes were unknown until recently.
2. The proliferation of new lymphatic vessels (lymphangiogenesis) is controlled, in part, by members of the vascular endothelial growth factor (VEGF) family — namely, VEGFC and VEGFD — and their cognate receptor on lymphatic endothelium, VEGFR3. These secreted growth factors are synthesized as propeptides that are activated by proteolysis to form high-affinity ligands that activate VEGFR3 and stimulate lymphangiogenesis.
3. The recent identification of molecular markers to discriminate between lymphatic endothelium and blood-vessel endothelium has enabled the study of lymphatic vessel formation in experimental models and in human tumours.
4. Experimental studies with VEGFC and VEGFD have shown that they can induce tumour lymphangiogenesis and direct metastasis to the lymphatic vessels and lymph nodes. By contrast, angiogenic factors such as VEGF act to enhance the growth of tumours by promoting a more extensive blood-vessel supply.
5. The published patterns of expression of lymphangiogenic factors in human tumours, in general, support the hypothesis that these factors promote the lymphatic spread of human tumours.
6. The inhibition of tumour lymphangiogenesis, using inhibitory agents that are directed to VEGFC, VEGFD or its receptor VEGFR3 (for example, monoclonal antibodies, receptor bodies or tyrosine kinase inhibitors), could be useful for anti-metastatic approaches to the treatment of human cancer.

要点翻译：

1. 肿瘤转移至区域淋巴结是癌症进展中的关键步骤。检测淋巴结中的肿瘤细胞是肿瘤扩散的标志，临床上将其作为预后判断工具和治疗指导依据。然而，控制癌症向淋巴结扩散的分子机制直到最近才得以揭示。
2. 新生淋巴管（淋巴管生成）的增殖部分受血管内皮生长因子（VEGF）家族成员——即VEGFC和VEGFD——及其在淋巴内皮上的同源受体VEGFR3的调控。这些分泌型生长因子以前肽形式合成，经蛋白水解激活后形成高亲和力配体，进而激活VEGFR3并刺激淋巴管生成。
3. 近期通过分子标记物区分淋巴内皮与血管内皮的技术突破，使得在实验模型和人类肿瘤中研究淋巴管形成成为可能。
4. 对VEGFC和VEGFD的实验研究表明，这些因子能够诱导肿瘤淋巴管生成，并直接导向淋巴管和淋巴结的转移。相比之下，VEGF等血管生成因子则是通过促进更密集的血管供应来增强肿瘤生长。
5. 目前已发表的人类肿瘤中淋巴管生成因子的表达模式，总体上支持这些因子促进人类肿瘤淋巴扩散的假说。
6. 通过针对VEGFC、VEGFD或其受体VEGFR3的抑制剂（如单克隆抗体、受体拮抗剂或酪氨酸激酶抑制剂）来抑制肿瘤淋巴管生成，可能为人类癌症的抗转移治疗提供新策略。

英文摘要：

Lymphatic vessels are important for the spread of solid tumours, but the mechanisms that underlie lymphatic spread and the role of lymphangiogenesis (the growth of lymphatics) in tumour metastasis has been less clear. This article reviews recent experimental and clinico-pathological data indicating that growth factors that stimulate lymphangiogenesis in tumours are associated with an enhanced metastatic process.

摘要翻译： 

淋巴管对实体瘤的播散至关重要，但其播散机制及淋巴管生成（淋巴管生长）在肿瘤转移中的作用一直不甚明了。本文综述了最新实验及临床病理资料，显示肿瘤中刺激淋巴管生成的生长因子与转移过程增强相关。

原文链接：

Lymphangiogenesis and cancer metastasis