VEGF-C and lymphatic vessels: a double-edged sword in tumor development and metastasis

The lymphatic system is made up of vessels that drain interstitial fluids throughout the body. The circulation of the lymph (liquid in the lymphatic system) in the lymphatic vessels is unidirectional: tissues to the lymph nodes and them to the veins. Ganglia are mechanical filters but also immune barriers that can block the progression of certain pathogens as well as cancer cells. However, most studies on the lymphatic system and cancer highlight the role of the lymphatic network in metastatic dissemination as tumor cells use this network to reach other organs. However, recent studies describe a beneficial role of the lymphatic system and of the vascular endothelial growth factor C (VEGF-C) which is one of the main factors responsible for the development of lymphatic vessels in cancer. In this review, we will illustrate this ambivalent and emerging role of VEGF-C and the lymphatic system in cancer aggressiveness.