Targeting the sphingosine-1-phosphate axis in cancer, inflammation and beyond
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TLDR
The ways in which S1P might be therapeutically targeted are discussed — for example, via the development of chemical inhibitors that target the generation, transport and degradation of S 1P and via thedevelopment of specific S1p receptor agonists.Abstract:
The bioactive lipid sphingosine-1-phosphate (S1P) is involved in multiple cellular signalling systems and has a pivotal role in the control of immune cell trafficking. As such, S1P has been implicated in disorders such as cancer and inflammatory diseases. This Review discusses the ways in which S1P might be therapeutically targeted — for example, via the development of chemical inhibitors that target the generation, transport and degradation of S1P and via the development of specific S1P receptor agonists. We also highlight recent conflicting results observed in preclinical studies targeting S1P and discuss ongoing clinical trials in this field.read more
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References
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Journal ArticleDOI
Anti-sphingosine-1-phosphate monoclonal antibodies inhibit angiogenesis and sub-retinal fibrosis in a murine model of laser-induced choroidal neovascularization
Sergio Caballero,James Stephen Swaney,Kelli Moreno,Aqeela Afzal,Jennifer L. Kielczewski,Glenn L. Stoller,Amy L. Cavalli,William A. Garland,Genevieve Hansen,Roger A. Sabbadini,Maria B. Grant +10 more
TL;DR: It is suggested that neutralizing S1P with anti-S1P mAbs may be a novel method of treating patients with exudative age-related macular degeneration by reducing angiogenesis and sub-retinal fibrosis, which are responsible for visual acuity loss in this disease.
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Sphingosine 1-Phosphate Receptor 4 Uses HER2 (ERBB2) to Regulate Extracellular Signal Regulated Kinase-1/2 in MDA-MB-453 Breast Cancer Cells
Jaclyn S. Long,Yuko Fujiwara,Joanne Edwards,Claire L. Tannahill,Gabor Tigyi,Susan Pyne,Nigel J. Pyne +6 more
TL;DR: The magnitude of the signaling gain on the ERK-1/2 pathway produced in response to S1p can be increased by HER2 in MDA-MB-453 cells, suggesting that S1P and EGF function in a mutually exclusive manner.
Journal ArticleDOI
Efficacy of a novel sphingosine kinase inhibitor in experimental Crohn’s disease
TL;DR: Sphingosine kinase may be a critical mediator of colonic damage during intestinal inflammation, and pharmacologic inhibitors of this enzyme may prove useful in the treatment of Crohn’s disease.
Journal ArticleDOI
Genetic Sphingosine Kinase 1 Deficiency Significantly Decreases Synovial Inflammation and Joint Erosions in Murine TNF-α–Induced Arthritis
DeAnna A. Baker,Jeremy L. Barth,Raymond Chang,Lina M. Obeid,Gary S. Gilkeson,Gary S. Gilkeson +5 more
TL;DR: Data indicate that SphK1 plays a key role in hTNF-α–induced inflammatory arthritis via impacting synovial inflammation and osteoclast number.
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Translational aspects of sphingosine 1-phosphate biology
Susan Pyne,Nigel J. Pyne +1 more
TL;DR: Fundamental aspects of S1P biology are described with an emphasis on the translational potential of intervention therapeutics and a major focus of research is to develop small-molecule antagonists/agonists/inhibitors that are specific to the different S 1P receptor subtypes and the enzymes that regulate S1p levels.