Skip to main content

Identification, characterization and mechanisms of action of new tumor-associated lymphangiogenesis inhibitors

Final Report Summary - TUMORLYMPHAINHIBIT (Identification, characterization and mechanisms of action of new tumor-associated lymphangiogenesis inhibitors)

The lymphatic vascular system is implicated in the maintenance of interstitial fluid homeostasis, is essential for the intestinal dietary fat and vitamin absorption and is required for the trafficking of immune cells and immune surveillance. Abnormalities of the lymphatic vasculature are involved in several human pathologies. Lymphangiogenesis or the formation of new lymphatic vessels from preexisting ones is a process very active during several pathological conditions. Defects in lymphatic function can lead to lymph and fat deposition in tissues, impaired immune responses and tissue swelling, known as lymphedema. In sharp contrast, an excessive lymphangiogenesis is crucially involved in various chronic inflammatory situations, graft rejection and metastatic dissemination.
In this project, we have discovered two new natural compounds as lymphangiogenic inhibitors and provided their cellular and molecular mechanisms of action. These compounds interfere with different crucial lymphangiogenic steps in in vitro, ex vivo and in vivo models and they affect the VEGF-C/VEGFR-3 axis, the best known signaling pathway in lymphangiogenesis. The promising properties of these new drugs pave the way for future pre-clinical and clinical studies. In addition, we have been set up new lymphangiogenic models that are suitable to better understand how cancer cells spread through the lymphatic vasculature to colonize the draining lymph nodes. Altogether, our work contributes to a better understanding of the complex lymphangiogenic process.