Tesis doctoral de Mª Dolores Salvado Duro
Prostanoids regulate angiogenesis in carcinoma and chronic inflammatory disease progression. While inducible expression of cox-2 and terminal prostaglandin synthases (tpgss) has been mainly analyzed in tumor, stromal and inflammatory cells, little is known about the regulation of prostanoid biosynthesis by the vascular compartment. Here we characterized the prostanoid biosynthesis of pge2, pgi2 and txa2 in activated endothelial cells. Although vegf and il-1b enhanced the endothelial prostanoid production, we failed to detect any parallel up-regulated expression nor enzymatic activation of endothelial tpgss. Hence, prostanoid levels increased concomitantly to cox-2 induction, and were abolished by cox-2 silencing or selective inhibition, suggesting a preferential functional coupling between cox-2 and tpgss. Furthermore, the endothelium-released cox-2-derived pgh2 can be transcellularly metabolized to pge2 by mpges-1 of neighboring tumor cells. These results highlight a major role for endothelial cox-2 as the limiting step in the biosynthesis of prostanoids and define a novel tumor-endothelium transcellular metabolism of pge2.
Datos académicos de la tesis doctoral «Regulation of prostanoid biosynthesis by human endothelial cells in angiogenesis: role of cox-2 in the intracellular and transcellular synthesis of prostanoids«
- Título de la tesis: Regulation of prostanoid biosynthesis by human endothelial cells in angiogenesis: role of cox-2 in the intracellular and transcellular synthesis of prostanoids
- Autor: Mª Dolores Salvado Duro
- Universidad: Autónoma de Madrid
- Fecha de lectura de la tesis: 24/10/2008
Dirección y tribunal
- Director de la tesis
- Juan Miguel Redondo
- Tribunal
- Presidente del tribunal: manuel Fresno escudero
- Luis Vila navarro (vocal)
- marina Ziche (vocal)
- dieter Steinhiber (vocal)