TUMORLYMPHAINHIBIT · Identification, characterization and mechanisms of action of new tumor-associated lymphangiogenesis inhibitors
FP7 — People (Marie Curie Actions)
- Duration
- 2014-04-01 → 2016-03-31
- EU contribution
- €169,800
- Participants
- 1
- Scheme
- MC-IEF
Lines connect the coordinator with its partners.
Results in brief
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.
Data: CORDIS, © European Union
Project objective
Cancer and tumor metastasis is the largest single cause of death in both, men and women, claiming over 7 million lives each year worldwide and, it is expected that by 2020 the number of dead cancer patients will grow to 10 million per year. Metastatic tumor cells utilize blood and lymphatic vessels as routes for dissemination and it is well known that lymphatic vasculature serves as a major route for tumor metastasis. Besides, lymphangiogenesis, the new lymphatic vessels formation from pre-existing ones, is pivotal for cancer cells spreading from primary sites to lymph nodes and, further, to distant tissues. Consequently, the search and identification of new tumor-induced lymphangiogenesis inhibitors and the understanding of their mechanisms of action, are a hot topic in the field of pharmacological research. In the present project, the applicant will finished the characterization of two marine compounds, toluquinol and AD0157, started during a short stay in the host institute. Preliminary results have shown that both compounds have excellent antilymphangiogenic properties in in vitro and ex vivo assays and, in the course of the present project they will be tested in in vivo models and their molecular targets will be revealed. Furthermore, other two new marine compounds will be analyzed in in vitro, ex vivo and in vivo experimental approaches. In these studies the applicant will focus in the behavior of the lymphatic endothelial tip and stalk cells, in order to shed light on their morphological and biochemical features. Hence, this project will increase significantly the acquisition of innovative knowledge on lymphangiogenesis phenomenon, on the different lymphatic endothelial tip/stalk cells features and on the cellular and molecular mechanisms of action of some natural compounds to inhibit tumor-related lymphangiogenesis. Those compounds with excellent antilymphangiogenic properties will be patented in order to be commercially exploitable as antitumor drugs.
Original text from CORDIS.
Participants
- UNIVERSITE DE LIEGE · LIEGECoordinatorBelgium
Links
Data: CORDIS, © European Union