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Sphingosine 1-Phosphate in Development and Diseases
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Sphingosine 1-Phosphate in Development and Diseases

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Pathology".

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 4514

Special Issue Editor

Dr. Burkhard Kleuser

E-Mail Website
Guest Editor
Institute of Pharmacy, Pharmacology and Toxicology, Freie Universität Berlin, Berlin, Germany
Interests: sphingolipids; diabetes; infection; epigenetics

Special Issue Information

Dear Colleagues,

Over 20 years ago, sphingosine 1-phosphate (S1P) was discovered as a novel bioactive molecule that regulates a variety of cellular functions such as embryonic development, postnatal organ function, and disease. The plethora of S1P-mediated effects is due to the fact that the sphingolipid not only modulates intracellular functions but also acts as a ligand of G protein-coupled receptors after secretion into the extracellular environment. To date, five high-affinity receptors for S1P, designated S1PR1-S1PR5, have been identified. Sphingosine kinases (SphK) are fine-tuned enzymes responsible for the formation of S1P as they catalyze the phosphorylation of sphingosine. Two isoforms of SphK have been discovered, named type 1 and 2, both of which are widely expressed and therefore regulate the level of S1P. In the plasma, S1P is found in high concentrations, modulating immune cell trafficking and vascular endothelial integrity. S1P research has grown exponentially since the first S1P receptor modulator, fingolimod, was employed as a human therapeutic for the treatment of multiple sclerosis in 2010. Today, it is well established that S1P is a critical player not only in immunology but also in inflammation, infection, cancer, as well as in cardiovascular and metabolic disorders. Further knowledge around the biology and metabolism of S1P is anticipated to further understand the role of this lipid molecule in a variety of pathophysiological conditions.

In this Special Issue of Cells, I invite you to contribute original research articles, reviews, or shorter perspective articles on all aspects related to the theme of “Sphingosine 1-phosphate in Development and Diseases”. Expert articles describing molecular, cellular, biochemical, physiological, pathophysiological, or general aspects of S1P, S1P-signaling, or S1P-metabolism are highly welcome. 

Dr. Burkhard Kleuser
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • S1P-receptors
  • sphingosine
  • sphingosine kinases
  • hexadecenal

Published Papers (2 papers)

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Research

16 pages, 4628 KiB  
Article
SPHK/HIF-1α Signaling Pathway Has a Critical Role in Chrysin-Induced Anticancer Activity in Hypoxia-Induced PC-3 Cells
by Hengmin Han, Seon-Ok Lee, Yinzhu Xu, Jung-Eun Kim and Hyo-Jeong Lee
Cells 2022, 11(18), 2787; https://doi.org/10.3390/cells11182787 - 7 Sep 2022
Cited by 9 | Viewed by 2162
Abstract
Hypoxia, a typical feature of locally advanced solid tumors including prostate cancer, is a critical contributor to tumor progression and causes resistance to therapy. In this study, we investigated the effects of chrysin on tumor progression in hypoxic PC-3 cells. Chrysin exerted a [...] Read more.
Hypoxia, a typical feature of locally advanced solid tumors including prostate cancer, is a critical contributor to tumor progression and causes resistance to therapy. In this study, we investigated the effects of chrysin on tumor progression in hypoxic PC-3 cells. Chrysin exerted a significant inhibitory effect on 3D cell growth under normoxic and hypoxic conditions. It also decreased the hypoxia-induced vasculogenic mimicry and attenuated the expression of HIF-1α and VE-cadherin. Chrysin inhibited HIF-1α accumulation in a concentration- and time-dependent manner in hypoxic PC-3 cells, while also suppressing the expression of HIF-1α by inhibiting SPHK-1 in both CoCl2 and hypoxic PC-3 cells. At high concentrations of chrysin, there was a greater increase in apoptosis in the hypoxic cells compared to that in normoxic cells, which was accompanied by sub-G1 phase arrest. Chrysin-induced apoptosis inhibited VEGF and Bcl-2 and induced the cleavage of PARP and caspase-3. SPHK-1 knockdown induced apoptosis and inhibited epithelial–mesenchymal transition. Consistent with the in vitro data, 50 mg/kg of chrysin suppressed the tumor growth of PC-3 xenografts by 80.4% compared to that in the untreated control group. The immunohistochemistry of tumor tissues revealed decreased Ki-67, HIF-1α, and VEGF expression in the chrysin-treated group compared to an untreated control. Western blotting data for tumor tissues showed that chrysin treatment decreased SPHK-1, HIF-1α, and PARP expression while inducing caspase-3 cleavage. Overall, our findings suggest that chrysin exerts anti-tumor activity by inhibiting SPHK-1/HIF-1α signaling and thus represents a potent chemotherapeutic agent for hypoxia, which promotes cancer progression and is related to poor prognoses in prostate cancer patients. Full article
(This article belongs to the Special Issue Sphingosine 1-Phosphate in Development and Diseases)
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13 pages, 2707 KiB  
Article
S1P-Induced TNF-α and IL-6 Release from PBMCs Exacerbates Lung Cancer-Associated Inflammation
by Michela Terlizzi, Chiara Colarusso, Pasquale Somma, Ilaria De Rosa, Luigi Panico, Aldo Pinto and Rosalinda Sorrentino
Cells 2022, 11(16), 2524; https://doi.org/10.3390/cells11162524 - 15 Aug 2022
Cited by 7 | Viewed by 2003
Abstract
Sphingosine-1-phosphate (S1P) is involved in inflammatory signaling/s associated with the development of respiratory disorders, including cancer. However, the underlying mechanism/s are still elusive. The aim of this study was to investigate the role of S1P on circulating blood cells obtained from healthy volunteers [...] Read more.
Sphingosine-1-phosphate (S1P) is involved in inflammatory signaling/s associated with the development of respiratory disorders, including cancer. However, the underlying mechanism/s are still elusive. The aim of this study was to investigate the role of S1P on circulating blood cells obtained from healthy volunteers and non-small cell lung cancer (NSCLC) patients. To pursue our goal, peripheral blood mononuclear cells (PBMCs) were isolated and stimulated with S1P. We found that the administration of S1P did not induce healthy PBMCs to release pro-inflammatory cytokines. In sharp contrast, S1P significantly increased the levels of TNF-α and IL-6 from lung cancer-derived PBMCs. This effect was S1P receptor 3 (S1PR3)-dependent. The pharmacological blockade of ceramidase and sphingosine kinases (SPHKs), key enzymes for S1P synthesis, completely reduced the release of both TNF-α and IL-6 after S1P addition on lung cancer-derived PBMCs. Interestingly, S1P-induced IL-6, but not TNF-α, release from lung cancer-derived PBMCs was mTOR- and K-Ras-dependent, while NF-κB was not involved. These data identify S1P as a bioactive lipid mediator in a chronic inflammation-driven diseases such as NSCLC. In particular, the higher presence of S1P could orchestrate the cytokine milieu in NSCLC, highlighting S1P as a pro-tumor driver. Full article
(This article belongs to the Special Issue Sphingosine 1-Phosphate in Development and Diseases)
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