Esfingosina-1-fosfato y cánceres urológicos: identificando potenciales blancos terapéuticos en su etabolismo y señalización / Sphingosine-1-phosphate and urological cancers: identifying potential therapeutic targets in its metabolism and signalling

Los lípidos no sólo son moléculas estructurales de las membranas. Hay numerosos ejemplos de lípidos que median acciones fisiológicas dentro de las células. Específicamente, esfingolípidos como ceramida, esfingosina y esfingosina-1-fosfato (S1P) han sido involucrados en el control del crecimiento celular, la proliferación y la migración, todo lo cual se ha relacionado con el cáncer.Los efectos pro-apoptóticos de la ceramida y la esfingosina son revertidos por S1P. Por lo tanto, el destino de la célula puede ser modulada mediante el cambio de la proporción de estos esfingolípidos (el modelo reóstato). S1P promueve la proliferación celular, el crecimiento, la supervivencia, la migración, invasión y resistencia fármacos y radiación, en parte a través de receptores de membrana (S1PR1-5). La sobreexpresión de enzimas productoras de S1P y el aumento de los niveles de S1P se ha descrito en muchos tipos de cáncer, incluyendo cánceres urológicos. Por lo tanto, se pueden identificar posibles objetivos terapéuticos en el metabolismo y las vías de señalización de los esfingolípidos, cuya relevancia clínica debe ser determinada en futuros estudios.

Lipids are not only structural molecules of the membranes. There are numerous examples of lipids mediating physiologic actions within the cells. Specifically, sphingolipids like ceramide, sphingosine and sphingosine-1-phosphate (S1P) have been described to be involved in the control of cell growth, proliferation and migration, all of which has been linked to cancer. The pro-apoptotic effects of ceramide and sphingosine are opposed by S1P. Therefore, the fate of the cell can be modulated by changing the ratio of these sphingolipids (the rheostat model). S1P promotes cell proliferation, growth, survival, migration, invasion and resistance to drugs and radiation, in part mediated by S1P membrane receptors (S1PR1-5). Overexpression of S1P producing enzymes and increased S1P levels has been described in many cancers, including urological cancers. Therefore, potential therapeutic targets can be recognized in the metabolism and signaling pathways of sphingolipids and their clinical relevance have to be determined in future studies.

Sphingosine 1-phosphate as a novel immune regulator of dendritic cells.

Although originally described as an intracellular second messenger, sphingosine 1-phosphate (S1P) has recently been shown to be involved in several physiological and pathological functions as an extracellular mediator. S1P receptors are widely expressed and thought to regulate important functions in cell signalling. Recently, the role of S1P on the immune system has evoked great interest. In particular, several aspects of the effects on antigen-presenting cells (APCs) as dendritic cells (DC) in mice and humans have been reported. In this review, we focus on the role played by S1P on the DC system and its effects in immune-related pathological states.