Sphingosine 1-Phosphate (S1P) Receptors 1 and 2 Coordinately Induce Mesenchymal Cell Migration through S1P Activation of Complementary Kinase Pathways*

Quint, Patrick; Ruan, Ming; Pederson, Larry; Kassem, Moustapha; Westendorf, Jennifer J.; Khosla, Sundeep; Oursler, Merry Jo

doi:10.1074/jbc.m112.413583

Cited by 78 publications

(64 citation statements)

References 64 publications

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“…Some of them are in agreement with the principle that S1P is able to mobilize osteoclasts [77,78]. Others found that S1P production via SphK1 in osteoclasts and its secretion stimulates osteoblast migration and survival, which supports bone formation [79,80,81,82]. In a different study, the role of TGF-beta1 on osteoclast-mediated support of mineralization was investigated and revealed that S1P production was, however, not induced in osteoclasts upon TGF-beta1 stimulation [83].…”

Section: Function Of S1p In Bloodsupporting

confidence: 52%

Sphingosine 1-Phosphate in Blood: Function, Metabolism, and Fate

Thuy

Reimann

Hemdan

et al. 2014

Cell Physiol Biochem

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Sphingosine 1-phosphate (S1P) is a lipid metabolite and a ligand of five G protein-coupled cell surface receptors S1PR1 to S1PR5. These receptors are expressed on various cells and cell types of the immune, cardiovascular, respiratory, hepatic, reproductive, and neurologic systems, and S1P has an impact on many different pathophysiological conditions including autoimmune, cardiovascular, and neurodegenerative diseases, cancer, deafness, osteogenesis, and reproduction. While these diverse signalling properties of S1P have been extensively reviewed, the particular role of S1P in blood is still a matter of debate. Blood contains the highest S1P concentration of all body compartments, and several questions are still not sufficiently answered: Where does it come from and how is it metabolized? Why is the concentration of S1P in blood so high? Are minor changes of the high blood S1P concentrations physiologically relevant? Do blood cells and vascular endothelial cells that are constantly exposed to high blood S1P levels still respond to S1P via S1P receptors? Recent data reveal new insights into the functional role and the metabolic fate of blood-borne S1P. This review aims to summarize our current knowledge regarding the source, secretion, transportation, function, metabolism, and fate of S1P in blood.

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Section: Function Of S1p In Bloodsupporting

confidence: 52%

Sphingosine 1-Phosphate in Blood: Function, Metabolism, and Fate

Thuy

Reimann

Hemdan

et al. 2014

Cell Physiol Biochem

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“…S1PR1 mediates chemoattraction toward S1P in bone marrow, where S1P concentration is low. S1PR2 mediates chemorepulsion in the blood, where tS1P concentration is high [36]. S1PR1 activates the small G-protein Rac and induces positive chemotaxis.…”

Section: Introductionmentioning

confidence: 99%

The effect of the bioactive sphingolipids S1P and C1P on multipotent stromal cells – new opportunities in regenerative medicine

Marycz

Śmieszek

Jeleń

et al. 2015

Cellular and Molecular Biology Letters

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Sphingosine-1-phosphate (S1P) and ceramide-1-phosphate (C1P) belong to a family of bioactive sphingolipids that act as important extracellular signaling molecules and chemoattractants. This study investigated the influence of S1P and C1P on the morphology, proliferation activity and osteogenic properties of rat multipotent stromal cells derived from bone marrow (BMSCs) and subcutaneous adipose tissue (ASCs). We show that S1P and C1P can influence mesenchymal stem cells (MSCs), each in a different manner. S1P stimulation promoted the formation of cellular aggregates of BMSCs and ASCs, while C1P had an effect on the regular growth pattern and expanded intercellular connections, thereby increasing the proliferative activity. Although osteogenic differentiation of MSCs was enhanced by the addition of S1P, the effectiveness of osteoblast differentiation was more evident in BMSCs, particularly when biochemical and molecular marker levels were considered. The results of the functional osteogenic differentiation assay, which includes an evaluation of the efficiency of extracellular matrix mineralization (SEM-EDX), revealed the formation of numerous mineral aggregates in BMSC cultures stimulated with S1P. Our data demonstrated that in an appropriate combination, the bioactive sphingolipids S1P and C1P may find wide application in regenerative medicine, particularly in bone regeneration with the use of MSCs.

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“…36 Several lines of evidence have suggested that recruitment of FAK to focal adhesions has an important role in GPCR-mediated signal transduction. [37][38][39] For example, Gibbs et al 40 reported that S1P/S1PR1 interaction can significantly activate FAK and AKT and subsequently induce tumor proliferation in prostate cancer cells. Our findings demonstrate the capability of PAFR in activating PI3K/AKT signaling pathways, at least in part, by interacting with the FAK protein and stimulating its kinase activity.…”

Section: Discussionmentioning

confidence: 98%

Platelet-activating factor receptor-mediated PI3K/AKT activation contributes to the malignant development of esophageal squamous cell carcinoma

Lan

Zhang

et al. 2015

Oncogene

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Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies worldwide and occurs at a relatively high frequency in China, yet the mechanisms underlying its devastating outcome remain unclear. Here we report that platelet-activating factor receptor (PAFR), a type of G-protein-coupled receptor, was upregulated in ESCC tumors and cell lines, compared with controls; PAFR levels were positively correlated with ESCC clinical stages and survival time. Overexpression of PAFR promoted the malignant development of ESCC in vitro and in vivo, whereas depletion of PAFR suppressed these effects. Interestingly, PAFR was observed to activate PI3K/AKT (phosphatidylinositol 3-kinase/AKT) through the upregulation of FAK kinase activity. AKT-triggered nuclear factor-κB transcriptionally activated PAFR expression. This mutual positive regulation between PAFR and AKT was required for the aggressiveness of ESCC cells both in vitro and in vivo. Furthermore, treating mice bearing ESCC tumors with cholesterol-conjugated PAFR small interfering RNA effectively inhibited tumor progression and the expression of AKT-mediated oncogenic proteins. Taken together, we made the first demonstration that dysregulation of PAFR and the positive regulatory loop between PAFR and pAKT contribute to malignant progression of ESCC.

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Sphingosine 1-Phosphate (S1P) Receptors 1 and 2 Coordinately Induce Mesenchymal Cell Migration through S1P Activation of Complementary Kinase Pathways*

Cited by 78 publications

References 64 publications

Sphingosine 1-Phosphate in Blood: Function, Metabolism, and Fate

Sphingosine 1-Phosphate in Blood: Function, Metabolism, and Fate

The effect of the bioactive sphingolipids S1P and C1P on multipotent stromal cells – new opportunities in regenerative medicine

Platelet-activating factor receptor-mediated PI3K/AKT activation contributes to the malignant development of esophageal squamous cell carcinoma

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