Tumor and Lymph Node Lymphangiogenesis

Metastatic spread to lymph nodes represents the first step of dissemination for the majority of human cancers and serves as an important prognostic parameter. It has been recently found—in experimental tumor models—that tumors can actively induce lymphangiogenesis, the growth of tumor-associated lymphatic vessels, and that tumor lymphangiogenesis promotes metastasis to sentinel lymph nodes. The major tumor lymphangiogenesis factors involved are vascular endothelial growth factor (VEGF)-C, VEGF-D, and VEGF-A. Importantly, clinical studies have confirmed the correlation of tumor lymphangiogenesis and metastasis in many different types of human cancers. Our recent findings indicate that tumors also induce lymphangiogenesis in sentinel lymph nodes, often before the actual onset of metastasis, promoting tumor dissemination to distant lymph nodes and beyond. Based on these findings, lymphangiogenesis has become a new prognostic indicator and also a target for the prevention and treatment of lymphatic metastases.