VEGF-C-induced lymphangiogenesis in sentinel lymph nodes promotes tumor metastasis to distant sites
VEGF-C-induced lymphangiogenesis in sentinel lymph nodes promotes tumor metastasis to distant sites
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DOI：
10.1182/blood-2006-05-021758
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发表时间：
2007-02-01
期刊：
影响因子：
20.3
通讯作者：
Detmar, Michael
中科院分区：
文献类型：
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作者：
Hirakawa, Satoshi;Brown, Lawrence F.;Detmar, Michael
肿瘤转移到前哨淋巴结和远端淋巴结及其他部位的机制尚不清楚。我们培育了在皮肤中特异性表达血管内皮生长因子- c （VEGF-C）和绿色荧光蛋白的转基因小鼠，并在该模型中研究了化学诱导的皮肤癌的作用。我们发现，与VEF-A相反，VEGF-C不会增加原发肿瘤的生长，而是诱导前哨淋巴结内淋巴网络的扩张，甚至在转移发生之前。一旦转移细胞到达前哨淋巴结，这些部位的淋巴管生成程度增加。重要的是，在具有转移性前哨淋巴结的小鼠中，表达VEGF-C的肿瘤更有可能转移到其他器官，如远端淋巴结和肺。在没有淋巴结转移的情况下，未观察到远处器官的转移。这些发现表明vegf - c诱导的淋巴结淋巴管生成在促进癌症转移到前哨淋巴结之外的重要作用。因此，VEGF-C是减缓甚至阻止转移发生的一个很好的靶点。
The mechanisms by which tumors metastasize to sentinel and distant lymph nodes, and beyond, are poorly understood. We developed transgenic mice that overexpress vascular endothelial growth factor-C (VEGF-C) and green fluorescent protein specifically in the skin and studied the effects of chemically-induced skin carcinogenesis in this model. We found that in contrast to VEF-A, VEGF-C does not increase the growth of primary tumors, but instead induces expansion of lymphatic networks within sentinel lymph nodes, even before the onset of metastasis. Once the metastatic cells arrived at the sentinel lymph nodes, the extent of lymphangiogenesis at these sites increased. Of importance, in mice with metastasis-containing sentinel lymph nodes, tumors that expressed VEGF-C were more likely to metastasize to additional organs, such as distal lymph nodes and lungs. No metastases were observed in distant organs in the absence of lymph node metastases. These findings indicate an important role of VEGF-C-induced lymph node lymphangiogenesis in the promotion of cancer metastasis beyond the sentinel lymph nodes. VEGF-C is therefore a good target to slow or even prevent the onset of metastasis.