Sphingosin 1-phosphate contributes in tumor progression

Tabasinezhad, Maryam; Samadi, Nasser; Ghanbari, Parisa; Mohseni, Masood; Saei, Amir Ata; Sharifi, Simin; Saeedi, Nazli; Pourhassan, Abolfazl

doi:10.4103/0973-1482.126446

Cited by 43 publications

(16 citation statements)

References 140 publications

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“…S1P receptors are divided into five subtypes: S1PR1, S1PR2, S1PR3, S1PR4, and S1PR5, and S1PRs are differentially coupled to heterotrimeric G proteins and Rac or Rho to regulate various effectors, such as MAPKs 1, 14, 40, 41. Previous studies have shown that S1P‐SIPRs signaling can enhance cell proliferation and migration.…”

Section: Discussionmentioning

confidence: 99%

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Survival benefit of sphingosin‐1‐phosphate and receptors expressions in breast cancer patients

Cheng

Liao

et al. 2018

Cancer Medicine

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Sphingosine‐1‐phosphate (S1P) is a bioactive lipid that exerts various pathophysiological functions through binding to its receptor family (S1PRs). Since first report of the breast cancer (BCA) promoting function by S1P production (through the function of sphingosine kinases) and S1P/S1PR signaling, their antagonists have never been successfully progress to clinics after three decades. Taking advantage of bioinformatics linking to gene expression to disease prognosis, we examined the impact of associated genes in BCA patients. We found high gene expressions involved in S1P anabolism suppressed disease progression of patients who are basal cell type BCA or receiving adjuvant therapy. In addition, S1PRs expression also suppressed disease progress of multiple categories of BCA patient progression. This result is contradictory to tumor promoter role of S1P/S1PRs which revealed in the literature. Further examination by directly adding S1P in BCA cells found a cell growth suppression function, which act via the expression of S1PR1. In conclusion, our study is the first evidence claiming a survival benefit function of S1P/S1PR signaling in BCA patients, which might explain the obstacle of relative antagonist apply in clinics.

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Section: Discussionmentioning

confidence: 99%

“…Sphingosine‐1‐phosphate (S1P) is a bioactive sphingolipid metabolite involved in many pathophysiological processes 1, 2, 3, 4. The intracellular level of S1P as a secondary messenger 5 is regulated by several enzymes including anabolism and catabolism.…”

Section: Introductionmentioning

confidence: 99%

Survival benefit of sphingosin‐1‐phosphate and receptors expressions in breast cancer patients

Cheng

Liao

et al. 2018

Cancer Medicine

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“…Similarly, S1P levels were decreased in plasma of sepsis patients and animal models of ALI (Winkler et al, 2015; Zhao et al, 2011) and infusion of S1P offered protection against LPS- and CLP-mediated lung inflammation and injury (Szczepaniak et al, 2008). In other lung pathologies such as asthma, pulmonary hypertension, pulmonary fibrosis, bronchopulmonary dysplasia, and lung cancer, S1P levels are elevated in plasma and in lung tissues of patients and animal models (Gairhe et al, 2016; Harijith et al, 2013; Huang & Natarajan, 2015; Jolly, Rosenfeldt, Milstien, & Spiegel, 2002; Tabasinezhad et al, 2013). Blocking S1P production by inhibiting sphingosine kinase (SPHK) 1 and/or 2 seems to offer protection against lung inflammation and injury in several lung disorders (Ebenezer, Fu, & Natarajan, 2016; Huang & Natarajan, 2015; Natarajan et al, 2013).…”

Section: Modulation Of Lung Endothelial Barrier Function By Inflammatmentioning

confidence: 99%

Sphingolipids Signaling in Lamellipodia Formation and Enhancement of Endothelial Barrier Function

Shaaya

Harijith

et al. 2018

Current Topics in Membranes

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Sphingolipids, first described in the brain in 1884, are important structural components of biological membranes of all eukaryotic cells. In recent years, several lines of evidence support the critical role of sphingolipids such as sphingosine, sphingosine-1-phosphate (S1P), and ceramide as anti- or pro-inflammatory bioactive lipid mediators in a variety of human pathologies including pulmonary and vascular disorders. Among the sphingolipids, S1P is a naturally occurring agonist that exhibits potent barrier enhancing property in the endothelium by signaling via G protein-coupled S1P1 receptor. S1P, S1P analogs, and other barrier enhancing agents such as HGF, oxidized phospholipids, and statins also utilize the S1P/S1P1 signaling pathway to generate membrane protrusions or lamellipodia, which have been implicated in resealing of endothelial gaps and maintenance of barrier integrity. A better understanding of sphingolipids mediated regulation of lamellipodia formation and barrier enhancement of the endothelium will be critical for the development of sphingolipid-based therapies to alleviate pulmonary disorders such as sepsis-, radiation-, and mechanical ventilation-induced acute lung injury.

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“…Immune cells such as lymphocytes, hematopoietic progenitor cells, and dendritic cells employ the S1P gradient to regulate their trafficking [ 5 ]. S1P is also involved in tumor progression [ 6 ], neoplastic cell proliferation [ 7 ], migration [ 8 ], and resistance to chemotherapeutic drugs [ 9 ]. In some malignancies, S1P overexpression is associated with poor prognosis [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

The novel sphingosine-1-phosphate receptors antagonist AD2900 affects lymphocyte activation and inhibits T-cell entry into the lymph nodes

et al. 2017

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Sphingolipid derivatives play key roles in immune cell migration and function. Synthetic sphingolipid analogues are used as therapeutics to intervene various inflammatory and malignant conditions. We hypothesize that different analogs have different effects on immune cells and therefore can be used as treatment for specific diseases. This study examines the properties of the novel synthetic sphingolipid analog, AD2900, and its effects on immune cell activation and lymphocyte localization in homeostasis. AD2900 is an antagonist for all sphingosine-1-phosphate (S1P) receptors. It demonstrates a significant inhibitory effect on the proliferation of activated human peripheral blood mononuclear cells, which is dependent on cAMP reduction and calcium signal transduction but not on phospholipase C activation. AD2900 causes a significant but reversible downregulation of S1P1 expression on the cell surface. AD2900 administration to C57BL/6J mice leads to the accumulation of T cells in the blood and spleen and in turn reduces T-cell number in the lymph nodes. Moreover, AD2900 treatment shows significant effects on the localization of T-cell subpopulations. These results demonstrate the key roles of S1P in T-cell trafficking in a steady state and suggest a potential clinical application for AD2900. Notably, this sphingolipid analog does not cause a severe lymphopenia. The clinical effect of AD2900 in hemato-oncologic diseases and immune-related diseases needs further investigation.

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Sphingosin 1-phosphate contributes in tumor progression

Cited by 43 publications

References 140 publications

Survival benefit of sphingosin‐1‐phosphate and receptors expressions in breast cancer patients

Survival benefit of sphingosin‐1‐phosphate and receptors expressions in breast cancer patients

Sphingolipids Signaling in Lamellipodia Formation and Enhancement of Endothelial Barrier Function

The novel sphingosine-1-phosphate receptors antagonist AD2900 affects lymphocyte activation and inhibits T-cell entry into the lymph nodes

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