Lymphangiogenesis and lymphatic metastasis in breast cancer.
Lymphangiogenesis and lymphatic metastasis in breast cancer.
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DOI：
10.1016/j.pathophys.2009.11.003
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发表时间：
2010-09
期刊：
影响因子：
--
通讯作者：
Flister MJ
中科院分区：
文献类型：
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作者：
Ran S;Volk L;Hall K;Flister MJ
淋巴结转移是乳腺癌和其他上皮性恶性肿瘤患者生存的主要预后因素。越来越多的临床和实验数据表明，淋巴管生成极大地促进了肿瘤细胞迁移到淋巴结中，淋巴管生成是一个在循环淋巴内皮祖细胞的帮助下从现有淋巴管产生新淋巴管的过程。诱导淋巴管生成的关键蛋白是血管内皮生长因子受体-3（VEGFR-3），其由血管内皮生长因子-C和-D（VEGF-C和VEGF-D）激活。这些淋巴管生成因子通常在恶性、肿瘤浸润和基质细胞中表达，为新淋巴管的生成创造了有利的环境。临床证据表明，肿瘤内和周围淋巴管密度增加与淋巴转移和患者生存率降低有关。最近的证据表明，乳腺癌诱导局部淋巴管和前哨淋巴结和远端淋巴结中的区域淋巴网络的重塑。这些变化包括肿瘤引流淋巴管的数量和直径增加。因此，远离肿瘤的淋巴流增加，这显著增加了肿瘤细胞转移到引流淋巴结，并可能导致全身扩散。总的来说，肿瘤诱导的淋巴管生成生物学的最新进展表明，该过程的化学抑制剂可能是抑制肿瘤转移和癌症相关死亡的有吸引力的靶点。然而，这是一个相对较新的研究领域，在肿瘤诱导的淋巴管生成的概念被接受为可行的抗转移靶点之前，还有很多工作要做。本文综述了目前有关乳腺癌淋巴管生成和淋巴转移的概念，同时强调了争议和未回答的问题。
Lymphatic metastasis is the main prognostic factor for survival of patients with breast cancer and other epithelial malignancies. Mounting clinical and experimental data suggest that migration of tumor cells into the lymph nodes is greatly facilitated by lymphangiogenesis, a process that generates new lymphatic vessels from pre-existing lymphatics with the aid of circulating lymphatic endothelial progenitor cells. The key protein that induces lymphangiogenesis is vascular endothelial growth factor receptor-3 (VEGFR-3), which is activated by vascular endothelial growth factor-C and -D (VEGF-C and VEGF-D). These lymphangiogenic factors are commonly expressed in malignant, tumor-infiltrating and stromal cells, creating a favorable environment for generation of new lymphatic vessels. Clinical evidence demonstrates that increased lymphatic vessel density in and around tumors is associated with lymphatic metastasis and reduced patient survival. Recent evidence shows that breast cancers induce remodeling of the local lymphatic vessels and the regional lymphatic network in the sentinel and distal lymph nodes. These changes include an increase in number and diameter of tumor-draining lymphatic vessels. Consequently, lymph flow away from the tumor is increased, which significantly increases tumor cell metastasis to draining lymph nodes and may contribute to systemic spread. Collectively, recent advances in the biology of tumor-induced lymphangiogenesis suggest that chemical inhibitors of this process may be an attractive target for inhibiting tumor metastasis and cancer-related death. Nevertheless, this is a relatively new field of study and much remains to be established before the concept of tumor-induced lymphangiogenesis is accepted as a viable anti-metastatic target. This review summarizes the current concepts related to breast cancer lymphangiogenesis and lymphatic metastasis while highlighting controversies and unanswered questions.