Molecular mechanisms of lymphangiogenesis in health and disease.

Studies of the last decades have revealed the importance of angiogenesis for normal growth and for the pathogenesis of numerous diseases. Much less studied is lymphangiogenesis, the growth of lymphatic vessels, which drain extravasated fluid, proteins, and cells and transport them back to the venous circulation. Nonetheless, insufficient lymphangiogenesis causes incapacitating lymphedema, while lymphatic growth around tumors may facilitate metastatic spread of malignant cells that ultimately kill the patient. The recent discovery of the key lymphangiogenic factors VEGF-C and VEGF-D and their receptor VEGFR-3 has allowed novel insights into how the lymphatic vessels and blood vessels coordinately grow and affect human disease. In addition, these studies have opened novel diagnostic and therapeutic avenues for the treatment of lymphedema and metastasis. This overview highlights the recent insights and developments in the field of lymphatic vascular research.