Tumor lymphangiogenesis and lymphangiogenic growth factors.

Recent studies have revealed that malignant tumors can actively induce the formation of new lymphatic vessels and metastasize through the lymphatic system. Tumor-induced lymphangiogenesis driven by tumors expressed lymphangiogenic growth factors such as VEGF family, fibroblast growth factor 2 (FGF-2), angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), and platelet-derived growth factors (PDGFs) is correlated with lymph node metastasis in experimental cancer models and in several types of human cancers. Tumor- induced lymphangiogenesis has now been firmly established as a novel mechanism for cancer progression and lymph node metastasis. Recent studies indicate that blockade of the lymphangiogenic growth factors pathway inhibits tumor spread to lymph nodes and likely beyond. The potential effects of most of these newly identified lymphatic growth factors on tumor-induced lymphangiogenesis and lymph node metastasis remain to be further investigated. A number of questions remain to be answered concerning the potential efficacy of targeting at tumor-induced lymphangiogenesis for inhibiting tumor spread to lymph nodes.