NITRIC OXIDE SYNTHASE, CICLOOXYGENASE AND ARGINASE ARE INVOLVED IN TUMOR PROGRESSION MEDIATED BY ANGIOGENESIS

Abstract
Angiogenesis is an essential step for tumor growth and metastasis. Nitric oxide (NO), the product of nitric oxide synthase isoenzymes (NOS) action on arginine (Arg) and prostaglandins (PGs) originated by COX isoforms from arachidonic acid are important mediators of tumor neovascularization. Arginase (A) is another enzyme involved in this step of tumor progression and shares with NOS the same sustrate, Arg. Tumor angiogenesis can be promoted not only by soluble mediators but also by appropriate cells. Lymphocytes, from tumor draining lymph nodes (TDLN) as well as circulating macrophages, can contact tumor cells triggering positive or negative functions on tumor growth. We observed an up-regulation in neuronal and endothelial NOS isoforms expression in TDLN and demonstrated that the inhibition of NOS activity reduced neovascularization induced by TDLN cells. In addition, we have also studied the role of peritoneal macrophages obtained from tumor bearing mice in blood vessels formation and observed that they induce angiogensis "via" A metabolic products. We can conclude that pro tumorigenic actions are highlighted in immunocompetent cells from tumor bearers.

Key words
Oxido nítrico sintasa, ciclooxigenasa, arginasa, angiogénesis, ganglios linfáticos

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