Molecular Mechanisms of Lymph Node Metastasis

Abstract

Lymph node metastasis represents the first step of spread for most human cancers and serves as an important prognostic indicator. Recent studies have revealed that tumors can actively induce the growth of tumor-associated lymphatic vessels (lymphangiogenesis), thus promoting their metastasis to draining (sentinel) lymph nodes. Several tumor lymphangiogenesis factors have been identified, including vascular endothelial growth factor (VEGF)-C, VEGF-D, VEGF-A and hepatocyte growth factor. A large number of clinical studies have confirmed the correlation of tumor lymphangiogenesis and metastasis of different types of human cancers. Importantly, recent results indicate that tumors can also induce lymphatic vessel growth in sentinel lymph nodes, even before the onset of metastasis, and that lymph node lymphangiogenesis further promotes cancer spread to distant lymph nodes and to distant organs. Thus, in addition to its prognostic importance, lymphangiogenesis has become a new target for the prevention, treatment and imaging of lymph node metastases.