Coordinating Effect of VEGFC and Oleic Acid Participates to Tumor Lymphangiogenesis

In cancer, the lymphatic system is hijacked by tumor cells that escape from primary and metastasize to sentinel lymph nodes. Tumor lymphangiogenesis stimulated vascular endothelial growth factors-C (VEGFC) after binding its receptor VEGFR-3. However, how VEGFC cooperates with other molecules promote lymphatics has not been fully determined. We showed developed in tumoral lesions surrounding adipose tissue (AT). Interestingly, vessel density correlated an increase circulating free fatty acids (FFA) tumor-bearing mice. adipocyte-released FFA are uploaded (LEC) stimulate their sprouting. Lipidomic analysis identified monounsaturated oleic acid (OA) as major a context. OA transporters FATP-3, -6 CD36 were only upregulated on LEC presence of showing collaborative effect these molecules. stimulates β-oxidation LECs, leading increased AT lymphangiogenesis. Our results provide new insights dialogue between tumors adipocytes via identify key role for adipocyte-derived promotion lymphangiogenesis, revealing novel therapeutic opportunities inhibitors cancer.