Abstract
Dermatan sulfate (DS) is widespread in the extracellular matrix (ECM) of animal tissues. This glycosaminoglycan is characterized by a variable structure, which is reflected in the heterogeneity of its sulfation pattern. The sulfate groups are responsible for the binding properties of DS, which determine an interaction profile of this glycan. However, the detailed role of DS in biological processes such as the neoplasm is still poorly understood. The aim of the study was to assess the effects of the structural variants of DS on breast cancer cells. We found that DS isoforms from normal and fibrotic fascia as well as from intestinal mucosa were able to quickly induce oxidative stress in the cytoplasm and affect the mitochondrial function in luminal breast cancer cells. Moreover, the variants caused the necroptosis of the cells most likely via the first of these mechanisms. This death was responsible for a reduction in the viability and number of breast cancer cells. However, the dynamics and intensity of all of the DS variants-triggered effects were strongly dependent on the cell type and the structure of these molecules. The most pronounced activity was demonstrated by those variants that shared structural features with the DS from the tumor niche.
Highlights
Academic Editors: Piotr Dziegiel and Dermatan sulfate (DS) is a component of glycoproteins termed DS proteoglycans (PG), which are commonly spread in the extracellular matrix (ECM) of the majority of animal tissues
All of the isolated variants underwent a structural analysis that included estimating the two basic structural features of these compounds, i.e., their sulfation pattern and glucuronosyl epimerization level. The latter parameter was measured as the content of the GlcA-containing disaccharides that are assembled into blocks in the glycan chains, because such sections are a predominant form of the occurrence of this disaccharide unit in almost all of the DS chains [2]
All of the used DS variants markedly differ in respect to their composition as results from specific profiles or quantities of unsaturated disaccharides that were rescued from these molecules by chondroitinase ABC or chondroitinase AC I treatment, respectively (Figure 1 and Supplementary Figure S1)
Summary
Academic Editors: Piotr Dziegiel and Dermatan sulfate (DS) is a component of glycoproteins termed DS proteoglycans (PG), which are commonly spread in the extracellular matrix (ECM) of the majority of animal tissues. DS is a copolymer of two types of disaccharide units from which one is composed of N-acetylgalactosamine (GalNAc) and glucoronate (GlcA) residues while the other contains GalNAc and iduronate (IdoA) residues [1] The former unit is present in DS and in the chondroitin sulfate (CS) chains, in which it is the only structural element. The latter disaccharide is characteristic only for DS and is responsible for the great flexibility of chains of these GAG chains because of the more conformational elasticity of IdoA residue compared to its C5 epimer—GlcA one [2]. Another structural feature of DS, which is shared with the remaining sulfated
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