Furthermore, since VEGF-D plays a remarkable role in up-regulating lymphangiogenesis and regional lymph node metastasis, other researchers in our group has established the mouse lymph node metastasis model by transfecting high expression VEGF-D into LL/2 Lewis lung carcinoma cells, and found that VEGF-D mainly bind to VEGFR-3 in lymphatic endothelial cells in vivo [31], and further study demonstrated that VEGFR-3 contributes to autocrine effects through VEGF-D-LL/2 cells [20]. This evidence concerns the gene FLT4 and metastatic malignant neoplasm in the lymph nodes.