Molecular control of lymphatic metastasis
Molecular control of lymphatic metastasis
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DOI：
10.1196/annals.1413.020
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发表时间：
2008-01-01
期刊：
影响因子：
--
通讯作者：
Stacker, Steven A.
中科院分区：
文献类型：
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作者：
Achen, Marc G.;Stacker, Steven A.
肿瘤细胞的转移扩散是癌症最致命的方面，通常通过淋巴管系统发生。实验肿瘤模型和人类临床病理数据均表明实体瘤附近淋巴管的生长(淋巴管生成)通常与淋巴结转移有关。肿瘤附近淋巴管内皮细胞黏附特性的改变也可能促进淋巴管的转移。淋巴管生成生长因子可促进肿瘤淋巴管的形成和肿瘤细胞向淋巴结的转移。这些蛋白包括分泌的糖蛋白血管内皮生长因子-C(VEGFR-C)和血管内皮生长因子-D(VEGFR-D)，它们通过位于淋巴管内皮细胞上的同源受体酪氨酸激酶-3(VEGFR-3)发挥作用。已报道的其他促进肿瘤淋巴管生成和/或淋巴转移的信号分子包括血管内皮生长因子-A、血小板衍生生长因子-BB和肝细胞生长因子。然而，这些蛋白在不同肿瘤类型中对肿瘤淋巴管生成和淋巴转移的定量贡献还有待进一步研究。此外，趋化因子被认为在吸引肿瘤细胞和淋巴管相互作用方面发挥了作用。此外，最近有研究表明，原发肿瘤分泌的淋巴管生长因子可以在肿瘤细胞到达之前就在附近的淋巴结中诱导淋巴管生成，这可能会促进进一步的转移。本文概述了控制淋巴转移的分子机制，并讨论了抑制人类癌症这一过程的潜在治疗方法。
The metastatic spread of tumor cells is the most lethal aspect of cancer and often occurs via the lymphatic vasculature. Both experimental tumor models and human clinicopathologic data indicate that growth of lymphatic vessels (lymphangiogenesis) near solid tumors is often associated with lymph node metastasis. Changes in the adhesive properties of lymphatic endothelium near tumors may also facilitate metastatic spread via the lymphatics. Lymphangiogenic growth factors have been identified that promote formation of tumor lymphatics and metastatic spread of tumor cells to lymph nodes. These include the secreted glycoproteins vascular endothelial growth factor-C (VEGF-C) and VEGF-D, which act via their cognate receptor tyrosine kinase VEGF receptor-3 (VEGFR-3) located on lymphatic endothelial cells. Other signaling molecules that have been reported to promote lymphangiogenesis and/or lymphatic metastasis in cancer include VEGF-A, platelet-derived growth factor-BB, and hepatocyte growth factor. However, the quantitative contribution of these proteins to tumor lymphangiogenesis and lymphatic metastasis in different tumor types requires further investigation. In addition, chemokines are thought to play a role in attracting tumor cells and lymphatic vessels to each other. Moreover, it has recently been shown that lymphangiogenic growth factors secreted from a primary tumor can induce lymphangiogenesis in nearby lymph nodes, even before arrival of tumor cells, which may facilitate further metastasis. This article provides an overview of the molecular mechanisms that control lymphatic metastasis and discusses potential therapeutic approaches for inhibiting this process in human cancer.