VEGF-C,VEGF-D pathways and tumor lymphangiogenesis

Tumor metastasis to sentinel lymph nodes represents the first step of tumor dissemination in most human cancers and serves as a major prognostic indicator for disease progression.Recent studies have revealed that tumor lymphangiogenesisis correlated with lymph node metastasis in experimental cancer models and in several types of human Cancers.Metastatic tumor cells may continue to promote lymphatic vessel growth even after their metastasis to sentinel lymph nodes,likely promoting further cancer spread.Vascular endothelial growth factor-C(VEGF-C)and VEGF-D are the first specific lymphangiogenesis factor identified,and a large number of clinical studies have shown a correlation between tumor expression of VEGF-C or VEGF-D and lymph node metastasis.Additional tumor lymphangiogenesis factors have been recently identifled,including VEGF-A.Importantly,blockade of the VEGFR-3 pathway by specific antibodies,by soluble receptor constructs,and by small molecule kinase iubibitors efficiently inhibits experimental tumor lymphangiogenesis and metastasis and might also represent a novel therapeutic avenue for the treatment of human cancers. Key words: Tumor; Vascular endothelial growth factor-C; Vascular endothelial growth factor-D