Tumorigenesis and Neoplastic Progression Distinct Roles of Vascular Endothelial Growth Factor-D in Lymphangiogenesis and Metastasis
Tumorigenesis and Neoplastic Progression Distinct Roles of Vascular Endothelial Growth Factor-D in Lymphangiogenesis and Metastasis
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在人类癌症中，淋巴管生成因子血管内皮生长因子-D（VEGF-D）的表达与上调的淋巴管生成和区域淋巴结转移相关。在这里，我们使用Rip 1 Tag 2转基因小鼠模型胰腺（cid：1）-细胞癌变研究功能的作用，VEGF-D诱导淋巴管生成和肿瘤进展。在单一转基因Rip 1VEGF-D小鼠的（cid：1）细胞中表达VEGF-D导致岛周淋巴陷窝的形成，通常含有白细胞积聚和血液渗出。当这些小鼠与Rip 1 Tag 2小鼠杂交时，表达VEGF-D的肿瘤也表现出肿瘤周围淋巴管生成，淋巴细胞聚集和转移，并且它们经常发生淋巴结和肺转移。值得注意的是，VEGF-D表达肿瘤的肿瘤生长和微血管密度显著降低。我们的研究结果表明，VEGF-D诱导淋巴管生成，促进淋巴结和肺转移，
In human carcinomas, expression of the lymphangiogenic factor vascular endothelial growth factor-D (VEGF-D) correlates with up-regulated lymphangiogenesis and regional lymph node metastasis. Here, we have used the Rip1Tag2 transgenic mouse model of pancreatic (cid:1) -cell carcinogenesis to investigate the functional role of VEGF-D in the induction of lymphangiogenesis and tumor progression. Expression of VEGF-D in (cid:1) cells of single-transgenic Rip1VEGF-D mice resulted in the formation of peri-insular lymphatic lacunae, often containing leukocyte accumulations and blood hemorrhages. When these mice were crossed to Rip1Tag2 mice, VEGF-D-expressing tumors also exhibited peritumoral lymphangiogenesis with lymphocyte accumulations and hemorrhages, and they frequently developed lymph node and lung metastases. Notably, tumor outgrowth and blood microvessel density were significantly reduced in VEGF-D-expressing tumors. Our results dem-onstrate that VEGF-D induces lymphangiogenesis, promotes metastasis to lymph nodes and lungs,