E X PE R IM EN TA L C ELL R E S EA RC H
333 (2015 ) 165
Available online at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/yexcr
Editorial
Introduction to the ECR special issue on lysophospholipids in biology It is some 25 years since lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P), nature's simplest phospholipids, were discovered as signaling molecules acting on then-unknown cellsurface receptors. With the subsequent identification of a family of cognate G protein-coupled receptors (GPCRs), LPA and S1P have attracted increasing interest, not least because of their emerging roles in key biological functions and disease processes. This issue of Experimental Cell Research contains a number of mini-reviews that cover recent developments in the LPA and S1P fields of research. LPA and S1P receptors are among the most widely expressed members of the entire GPCR superfamily and, hence, almost every cell type is responsive to either lipid, or to both. LPA and S1P are best known for their stimulatory effects on cell migration, proliferation and cytoskeletal remodeling. Over time, the underlying signaling pathways have been delineated in molecular detail, while the use of knockout mice has greatly contributed to our current understanding of the biology of these lipid mediators. Although LPA and S1P often activate very similar signaling pathways, their respective biosynthetic routes are quite different. LPA is produced extracellularly from water-soluble lysophosphatidyl choline by a secreted lysophospholipase D, named autotaxin (ATX). In marked contrast, S1P is produced intracellularly through ATP-dependent phosphorylation and then secreted into the extracellular space. On the basis of animal studies, LPA and S1P have been implicated in a broad spectrum of physiological and pathophysiological processes such as vascular development, angiogenesis,
lymphocyte homing, wound healing, fibrosis, inflammation and tumor progression, to name just a few. Therefore, LPA and S1P receptors, as well as ATX, are attractive therapeutic targets and a number of small-molecule drug candidates are now in various stages of clinical development. The present mini-reviews cover select topics on the roles of LPA and S1P in angiogenesis, intestinal functions and tumor progression, as well as on development and in vivo imaging of S1P receptor activation in tissues and during inflammation. Future studies should lead to a better understanding of the biology of LPA and S1P and, furthermore, to identification of pathologies characterized by aberrant LPA/S1P production and signaling. New preclinical models and more clinical data will be needed to fully define the multiple roles of these fascinating lipid mediators in cell biology and disease processes.
Wouter H. Moolenaar The Netherlands Cancer Institute, Division of Cell Biology, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands E-mail address: [email protected] 0014-4827/$ - see front matter & 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.yexcr.2015.02.021
333 (2015 ) 165
Available online at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/yexcr
Editorial
Introduction to the ECR special issue on lysophospholipids in biology It is some 25 years since lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P), nature's simplest phospholipids, were discovered as signaling molecules acting on then-unknown cellsurface receptors. With the subsequent identification of a family of cognate G protein-coupled receptors (GPCRs), LPA and S1P have attracted increasing interest, not least because of their emerging roles in key biological functions and disease processes. This issue of Experimental Cell Research contains a number of mini-reviews that cover recent developments in the LPA and S1P fields of research. LPA and S1P receptors are among the most widely expressed members of the entire GPCR superfamily and, hence, almost every cell type is responsive to either lipid, or to both. LPA and S1P are best known for their stimulatory effects on cell migration, proliferation and cytoskeletal remodeling. Over time, the underlying signaling pathways have been delineated in molecular detail, while the use of knockout mice has greatly contributed to our current understanding of the biology of these lipid mediators. Although LPA and S1P often activate very similar signaling pathways, their respective biosynthetic routes are quite different. LPA is produced extracellularly from water-soluble lysophosphatidyl choline by a secreted lysophospholipase D, named autotaxin (ATX). In marked contrast, S1P is produced intracellularly through ATP-dependent phosphorylation and then secreted into the extracellular space. On the basis of animal studies, LPA and S1P have been implicated in a broad spectrum of physiological and pathophysiological processes such as vascular development, angiogenesis,
lymphocyte homing, wound healing, fibrosis, inflammation and tumor progression, to name just a few. Therefore, LPA and S1P receptors, as well as ATX, are attractive therapeutic targets and a number of small-molecule drug candidates are now in various stages of clinical development. The present mini-reviews cover select topics on the roles of LPA and S1P in angiogenesis, intestinal functions and tumor progression, as well as on development and in vivo imaging of S1P receptor activation in tissues and during inflammation. Future studies should lead to a better understanding of the biology of LPA and S1P and, furthermore, to identification of pathologies characterized by aberrant LPA/S1P production and signaling. New preclinical models and more clinical data will be needed to fully define the multiple roles of these fascinating lipid mediators in cell biology and disease processes.
Wouter H. Moolenaar The Netherlands Cancer Institute, Division of Cell Biology, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands E-mail address: [email protected] 0014-4827/$ - see front matter & 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.yexcr.2015.02.021
