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Search Results (3)

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Keywords = CD15s glycosphingolipid

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12 pages, 2509 KiB  
Article
Thieno[2,3-b]Pyridine Derivative Targets Epithelial, Mesenchymal and Hybrid CD15s+ Breast Cancer Cells
by Sandra Marijan, Angela Mastelić, Anita Markotić, Nikolina Režić-Mužinić, Nikolina Vučenović, David Barker, Lisa I. Pilkington, Jóhannes Reynisson and Vedrana Čikeš Čulić
Medicines 2021, 8(7), 32; https://doi.org/10.3390/medicines8070032 - 22 Jun 2021
Cited by 2 | Viewed by 4069
Abstract
The adhesion of cancer cells to vascular endothelium is a critical process in hematogenous metastasis and might be similar to the recruitment of leukocytes at the site of inflammation. It is mediated by E-selectin and its ligands, of which the most stereospecific is [...] Read more.
The adhesion of cancer cells to vascular endothelium is a critical process in hematogenous metastasis and might be similar to the recruitment of leukocytes at the site of inflammation. It is mediated by E-selectin and its ligands, of which the most stereospecific is a glycoconjugate sialyl Lewis x (CD15s), which may be expressed as an oligosaccharide branch of the CD44 glycoprotein, as well as a self-contained glycosphingolipid. It is also known that increased sialylation of glycoconjugates is a feature of malignant cells. The aim of the study was to analyse the effect of a novel thieno[2,3-b]pyridine, compound 1, in MDA-MB-231 triple-negative breast cancer cells (TNBCs) upon CD15s and CD44 expression in different cell subpopulations using flow cytometry. CD15s expression was compared between mesenchymal-like cancer stem cells (CSC, CD44+CD24−), epithelial cells without CD44 (CD44−CD24+ and CD44−CD24−), and CD44+CD24+ cells that exhibit mesenchymal and epithelial features. In addition, expression of CD44 in CD15s+CSC and CD15s−CSC was determined. Compound 1 significantly decreased the percentage of CD15s+CSC, CD15s+CD44+CD24+, and CD15s+CD44− subpopulations, as well as the expression of CD15s in CD44+CD24+ and CD44− cells, and therefore shows potential as a treatment for TNBC. Full article
(This article belongs to the Section Cancer Biology and Anticancer Therapeutics)
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19 pages, 16481 KiB  
Review
Shiga Toxins: An Update on Host Factors and Biomedical Applications
by Yang Liu, Songhai Tian, Hatim Thaker and Min Dong
Toxins 2021, 13(3), 222; https://doi.org/10.3390/toxins13030222 - 18 Mar 2021
Cited by 29 | Viewed by 7811
Abstract
Shiga toxins (Stxs) are classic bacterial toxins and major virulence factors of toxigenic Shigella dysenteriae and enterohemorrhagic Escherichia coli (EHEC). These toxins recognize a glycosphingolipid globotriaosylceramide (Gb3/CD77) as their receptor and inhibit protein synthesis in cells by cleaving 28S ribosomal RNA. They are [...] Read more.
Shiga toxins (Stxs) are classic bacterial toxins and major virulence factors of toxigenic Shigella dysenteriae and enterohemorrhagic Escherichia coli (EHEC). These toxins recognize a glycosphingolipid globotriaosylceramide (Gb3/CD77) as their receptor and inhibit protein synthesis in cells by cleaving 28S ribosomal RNA. They are the major cause of life-threatening complications such as hemolytic uremic syndrome (HUS), associated with severe cases of EHEC infection, which is the leading cause of acute kidney injury in children. The threat of Stxs is exacerbated by the lack of toxin inhibitors and effective treatment for HUS. Here, we briefly summarize the Stx structure, subtypes, in vitro and in vivo models, Gb3 expression and HUS, and then introduce recent studies using CRISPR-Cas9-mediated genome-wide screens to identify the host cell factors required for Stx action. We also summarize the latest progress in utilizing and engineering Stx components for biomedical applications. Full article
(This article belongs to the Special Issue Selected Papers from the 26th Meeting of the French Society for Toxinology—Bioengineering of Toxins)
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31 pages, 4838 KiB  
Article
Identification of Brain-Specific Treatment Effects in NPC1 Disease by Focusing on Cellular and Molecular Changes of Sphingosine-1-Phosphate Metabolism
by Anne Gläser, Franziska Hammerl, Markus H. Gräler, Sina M. Coldewey, Christin Völkner, Moritz J. Frech, Fan Yang, Jiankai Luo, Eric Tönnies, Oliver von Bohlen und Halbach, Nicola Brandt, Diana Heimes, Anna-Maria Neßlauer, Georg Christoph Korenke, Marta Owczarek-Lipska, John Neidhardt, Arndt Rolfs, Andreas Wree, Martin Witt and Anja Ursula Bräuer
Int. J. Mol. Sci. 2020, 21(12), 4502; https://doi.org/10.3390/ijms21124502 - 24 Jun 2020
Cited by 8 | Viewed by 4764
Abstract
Niemann–Pick type C1 (NPC1) is a lysosomal storage disorder, inherited as an autosomal-recessive trait. Mutations in the Npc1 gene result in malfunction of the NPC1 protein, leading to an accumulation of unesterified cholesterol and glycosphingolipids. Beside visceral symptoms like hepatosplenomegaly, severe neurological symptoms [...] Read more.
Niemann–Pick type C1 (NPC1) is a lysosomal storage disorder, inherited as an autosomal-recessive trait. Mutations in the Npc1 gene result in malfunction of the NPC1 protein, leading to an accumulation of unesterified cholesterol and glycosphingolipids. Beside visceral symptoms like hepatosplenomegaly, severe neurological symptoms such as ataxia occur. Here, we analyzed the sphingosine-1-phosphate (S1P)/S1P receptor (S1PR) axis in different brain regions of Npc1−/− mice and evaluated specific effects of treatment with 2-hydroxypropyl-β-cyclodextrin (HPβCD) together with the iminosugar miglustat. Using high-performance thin-layer chromatography (HPTLC), mass spectrometry, quantitative real-time PCR (qRT-PCR) and western blot analyses, we studied lipid metabolism in an NPC1 mouse model and human skin fibroblasts. Lipid analyses showed disrupted S1P metabolism in Npc1−/− mice in all brain regions, together with distinct changes in S1pr3/S1PR3 and S1pr5/S1PR5 expression. Brains of Npc1−/− mice showed only weak treatment effects. However, side effects of the treatment were observed in Npc1+/+ mice. The S1P/S1PR axis seems to be involved in NPC1 pathology, showing only weak treatment effects in mouse brain. S1pr expression appears to be affected in human fibroblasts, induced pluripotent stem cells (iPSCs)-derived neural progenitor and neuronal differentiated cells. Nevertheless, treatment-induced side effects make examination of further treatment strategies indispensable. Full article
(This article belongs to the Special Issue Sphingolipids: Metabolic Functions and Disorders)
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