Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis
Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis
复制标题
DOI：
10.1038/84643
复制
发表时间：
2001-02-01
期刊：
影响因子：
82.9
通讯作者：
Detmar, M
中科院分区：
文献类型：
--
作者：
Skobe, M;Hawighorst, T;Detmar, M
乳腺癌的转移主要通过淋巴系统发生，淋巴结受累的程度是该疾病的关键预后因素。尽管血管生成对肿瘤进展的重要性已被充分证明，但肿瘤细胞诱导淋巴管生长的能力（淋巴管生成）和肿瘤内淋巴管的存在一直存在争议。利用淋巴内皮的一种新的标志物LYVE-1，我们在这里证明了裸鼠原位移植后人乳腺癌肿瘤内淋巴管生成的发生。血管内皮生长因子(VEGF)-C在乳腺癌细胞中的过度表达可显著增加瘤内淋巴管生成，导致向区域淋巴结和肺转移的显著增强。肿瘤淋巴管生成程度与淋巴结及肺转移程度高度相关。这些结果确定了乳腺癌肿瘤内淋巴管生成的发生及其生物学意义，并确定VEGF-C是肿瘤淋巴管生成和转移之间的分子联系。
Metastasis of breast cancer occurs primarily through the lymphatic system, and the extent of lymph node involvement is a key prognostic factor for the disease. Whereas the significance of angiogenesis for tumor progression has been well documented, the ability of tumor cells to induce the growth of lymphatic vessels (lymphangiogenesis) and the presence of intratumoral lymphatic vessels have been controversial. Using a novel marker for lymphatic endothelium, LYVE-1, we demonstrate here the occurrence of intratumoral lymphangiogenesis within human breast cancers after orthotopic transplantation onto nude mice. Vascular endothelial growth factor (VEGF)-C overexpression in breast cancer cells potently increased intratumoral lymphangiogenesis, resulting in significantly enhanced metastasis to regional lymph nodes and to lungs. The degree of tumor lymphangiogenesis was highly correlated with the extent of lymph node and lung metastases. These results establish the occurrence and biological significance of intratumoral lymphangiogenesis in breast cancer and identify VEGF-C as a molecular link between tumor lymphangiogenesis and metastasis.