Vascular endothelial growth factor C promotes lymph node metastasis in a rectal cancer orthotopic model
Vascular endothelial growth factor C promotes lymph node metastasis in a rectal cancer orthotopic model
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DOI：
10.1007/s00595-004-2896-0
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发表时间：
2005-02-01
期刊：
影响因子：
2.5
通讯作者：
Hirata, K
中科院分区：
文献类型：
--
作者：
Kawakami, M;Yanai, Y;Hirata, K
目的。血管内皮生长因子C （Vascular endothelial growth factor C, VEGF-C）是血管内皮生长因子家族的新成员，是一种相对特异性的淋巴管生长因子。有研究表明，原发性肿瘤中VEGF-C的表达增加与淋巴结转移有关。本研究旨在确定VEGF-C是否直接影响结直肠癌的淋巴管生成和淋巴结转移。为了准确分析和清楚地显示转移，我们对直肠癌细胞系DLD1进行了工程改造，使其稳定表达绿色荧光蛋白（GFP） （DLD1/GFP）。我们将过表达VEGF-C的DLD1/GFP细胞原位植入裸鼠直肠壁。所有（100%）携带DLD1/GFP-VEGF-C肿瘤的小鼠均证实有淋巴结转移，而携带对照肿瘤的小鼠只有25%证实有淋巴结转移。每只携带DLD1/GFP-VEGF-C肿瘤的小鼠比携带对照肿瘤的小鼠有更多的淋巴结转移。两组之间在体外的细胞生长和运动性以及植入细胞产生的肿瘤体积方面没有差异。免疫组化染色显示VEGF-C诱导肿瘤周围淋巴管生长，淋巴管增大，并含有肿瘤细胞栓塞。这些结果提示vegf - c诱导的淋巴管生成介导肿瘤的扩散和淋巴结转移的形成。
Purpose. Vascular endothelial growth factor C (VEGF-C), a novel member of the vascular endothelial growth factor family, is a relatively specific lymphangiogenic growth factor. It has been suggested that increased expression of VEGF-C in primary tumors is correlated with lymph node metastasis. We conducted this study to determine whether VEGF-C directly affects lymphangiogenesis and lymph node metastasis in colorectal cancer.Methods. For an accurate analysis and clear visualization of metastases, the rectal cancer cell line, DLD1, was engineered to stably express green fluorescent protein (GFP) (DLD1/GFP). We implanted DLD1/GFP cells overexpressing VEGF-C orthotopically into the rectal walls of nude mice.Results. Lymph node metastasis was confirmed in all (100%) of the mice bearing DLD1/GFP-VEGF-C tumors, but in only 25% of the mice bearing control tumors. There were more lymph node metastases per mouse in the mice bearing DLD1/GFP-VEGF-C tumors than in the mice bearing control tumors. There were no differences in cell growth and motility in vitro or in the resulting tumor volume from the implanted cells between the two groups. Immunohistochemical staining revealed that VEGF-C induced the growth of lymphatic vessels, which were enlarged in the tumor periphery and contained tumor cell emboli.Conclusion. These results suggest that VEGF-C-induced lymphangiogenesis mediates tumor spread and the formation of lymph node metastasis.