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Article ; Online: Dermatan Sulfate Affects Breast Cancer Cell Function via the Induction of Necroptosis.

Wisowski, Grzegorz / Pudełko, Adam / Olczyk, Krystyna / Paul-Samojedny, Monika / Koźma, Ewa M

2022 Volume 11, Issue 1

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 ...

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.
MeSH term(s)	Animals ; Breast Neoplasms/pathology ; Cell Count ; Cell Death/drug effects ; Cell Line, Tumor ; Cell Survival/drug effects ; Dermatan Sulfate/pharmacology ; Female ; Humans ; Mitochondria/drug effects ; Mitochondria/metabolism ; Necroptosis/drug effects ; Oxidative Stress/drug effects
Chemical Substances	Dermatan Sulfate (24967-94-0)
Language	English
Publishing date	2022-01-05
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11010173
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Dermatan Sulfate Affects Breast Cancer Cell Function via the Induction of Necroptosis

Grzegorz Wisowski / Adam Pudełko / Krystyna Olczyk / Monika Paul-Samojedny / Ewa M. Koźma

Cells, Vol 11, Iss 173, p

2022 Volume 173

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.
Keywords	dermatan sulfate ; breast cancer cells ; necroptosis ; oxidative stress ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article: Plasma Glycosaminoglycans in Children with Juvenile Idiopathic Arthritis Being Treated with Etanercept as Potential Biomarkers of Joint Dysfunction.

Wojdas, Magdalena / Dąbkowska, Klaudia / Kuźnik-Trocha, Kornelia / Wisowski, Grzegorz / Lachór-Motyka, Iwona / Komosińska-Vassev, Katarzyna / Olczyk, Krystyna / Winsz-Szczotka, Katarzyna

Biomedicines

2022 Volume 10, Issue 8

Abstract: We assessed the effect of two-year etanercept (ETA) therapy on the metabolism of the cartilage extracellular matrix (ECM) in patients with juvenile idiopathic arthritis (JIA).: Methods: We performed a quantitative evaluation of glycosaminoglycans ( ... ...

Abstract	We assessed the effect of two-year etanercept (ETA) therapy on the metabolism of the cartilage extracellular matrix (ECM) in patients with juvenile idiopathic arthritis (JIA). Methods: We performed a quantitative evaluation of glycosaminoglycans (GAGs) (performed by the multistage extraction and purification method) in blood obtained from patients before and during 24 months of ETA treatment, as potential biomarker of joint dysfunction and indicators of biological effectiveness of therapy. Since the metabolism of GAGs is related to the activity of proteolytic enzymes and prooxidant-antioxidant factors, we decided to evaluate the relationship between GAGs and the levels of metalloproteinases (MMP), i.e., MMP-1 and MMP-3 (using immunoenzymatic methods), as well as the total antioxidative status (TAS) (using the colorimetric method) in blood of the JIA patients. Results: When compared to the controls, GAGs and TAS concentrations were significantly lower in patients with an aggressive course of JIA qualified for ETA treatment. MMP-1 and MMP-3 levels were significantly higher versus control values. An anti-cytokine therapy leading to clinical improvement does not lead to the normalization of any of the assessed parameters. GAGs concentration is significantly related to MMP-1, MMP-3, TAS, TOS, and CRP levels. Conclusion: The results of the present study indicate the necessity of constant monitoring of the dynamics of destructive processes of articular cartilage in children with JIA. We suggest that GAGs may be a useful biomarker to assess the clinical status of the extracellular matrix of joints.
Language	English
Publishing date	2022-07-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines10081845
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Article: GAAGs, COMP, and YKL-40 as Potential Markers of Cartilage Turnover in Blood of Children with Juvenile Idiopathic Arthritis Treated with Etanercept-Relationship with ADAMTS4, ADAMTS5, and PDGF-BB.

Dąbkowska, Klaudia / Wojdas, Magdalena / Kuźnik-Trocha, Kornelia / Wisowski, Grzegorz / Gruenpeter, Anna / Komosińska-Vassev, Katarzyna / Olczyk, Krystyna / Winsz-Szczotka, Katarzyna

Journal of clinical medicine

2022 Volume 11, Issue 17

Abstract: We quantified galactosaminoglycans (GAAGs), oligomeric cartilage matrix protein (COMP), and human cartilage glycoprotein 39 (YKL-40) in blood obtained from juvenile idiopathic arthritis (JIA) before and during 2-year treatment with etanercept (ETA), as ... ...

Abstract	We quantified galactosaminoglycans (GAAGs), oligomeric cartilage matrix protein (COMP), and human cartilage glycoprotein 39 (YKL-40) in blood obtained from juvenile idiopathic arthritis (JIA) before and during 2-year treatment with etanercept (ETA), as potential biomarkers of cartilage extracellular matrix (ECM) dysfunction and indicators of efficacy of biologic therapy. We also evaluated the relationship of the mentioned markers with the factors that regulate their metabolism, disintegrin and thrombospondin motif metalloproteinases 4 (ADAMTS4), ADAMTS5, and platelet-derived growth factor BB (PDGF-BB). Methods: We studied 38 children diagnosed with JIA and 45 healthy children. We quantified GAAGs by assessing the concentration of unsaturated disaccharide units formed by digestion of isolated glycosaminoglycans with chondroitinase ABC, while COMP, YKL-40, and PDGF-BB were quantified using immunoenzymatic methods. Results: Compared to the control group, GAAGs and COMP levels were significantly lower, while YKL-40 levels were higher in the blood of patients with aggressive JIA, qualified for ETA treatment. ETA therapy leading to clinical improvement simultaneously promoted normalization of COMP and YKL-40 levels, but not GAAGs. After 24 months of taking ETA, glycan levels were still significantly lower, relative to controls. GAAGs, COMP, and YKL-40 levels were significantly influenced by ADAMTS4, ADAMTS5, and PDGF-BB levels both before and during ETA treatment. Conclusions: The dynamics of changes in marker concentrations during treatment seem to indicate that measurement of COMP and YKL-40 levels can be used to assess the chondroprotective biological efficacy of therapy. In contrast, changes in GAAGs concentrations reflect systemic extracellular matrix transformations in the course of JIA.
Language	English
Publishing date	2022-08-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm11175069
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Article ; Online: The dual role of the glycosaminoglycan chondroitin-6-sulfate in the development, progression and metastasis of cancer.

Pudełko, Adam / Wisowski, Grzegorz / Olczyk, Krystyna / Koźma, Ewa Maria

The FEBS journal

2019 Volume 286, Issue 10, Page(s) 1815–1837

Abstract: The remarkable structural heterogeneity of chondroitin sulfate (CS) and dermatan sulfate (DS) generates biological information that can be unique to each of these glycosaminoglycans (GAGs), and changes in their composition are translated into alterations ...

Abstract	The remarkable structural heterogeneity of chondroitin sulfate (CS) and dermatan sulfate (DS) generates biological information that can be unique to each of these glycosaminoglycans (GAGs), and changes in their composition are translated into alterations in the binding profiles of these molecules. CS/DS can bind to various cytokines and growth factors, cell surface receptors, adhesion molecules, enzymes and fibrillar glycoproteins of the extracellular matrix, thereby influencing both cell behavior and the biomechanical and biochemical properties of the matrix. In this review, we summarize the current knowledge concerning CS/DS metabolism in the human cancer stroma. The remodeling of the GAG profile in the tumor niche is manifested as a substantial increase in the CS content and a gradual decrease in the proportion between DS and CS. Furthermore, the composition of CS and DS is also affected, which results in a substantial increase in the 6-O-sulfated and/or unsulfated disaccharide content, which is concomitant with a decrease in the 4-O-sulfation level. Here, we discuss the possible impact of alterations in the CS/DS sulfation pattern on the binding capacity and specificity of these GAGs. Moreover, we propose potential consequences of the stromal accumulation of chondroitin-6-sulfate for the progression and metastasis of cancer.
MeSH term(s)	Animals ; Chondroitin Sulfates/chemistry ; Chondroitin Sulfates/metabolism ; Dermatan Sulfate/chemistry ; Dermatan Sulfate/metabolism ; Humans ; Inflammation/metabolism ; Neoplasms/metabolism ; Neoplasms/pathology ; Stromal Cells/metabolism ; Stromal Cells/pathology ; Tumor Microenvironment
Chemical Substances	Dermatan Sulfate (24967-94-0) ; Chondroitin Sulfates (9007-28-7)
Language	English
Publishing date	2019-02-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2173655-8
ISSN	1742-4658 ; 1742-464X
ISSN (online)	1742-4658
ISSN	1742-464X
DOI	10.1111/febs.14748
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Article ; Online: GAAGs, COMP, and YKL-40 as Potential Markers of Cartilage Turnover in Blood of Children with Juvenile Idiopathic Arthritis Treated with Etanercept—Relationship with ADAMTS4, ADAMTS5, and PDGF-BB

Klaudia Dąbkowska / Magdalena Wojdas / Kornelia Kuźnik-Trocha / Grzegorz Wisowski / Anna Gruenpeter / Katarzyna Komosińska-Vassev / Krystyna Olczyk / Katarzyna Winsz-Szczotka

Journal of Clinical Medicine, Vol 11, Iss 5069, p

2022 Volume 5069

Abstract	We quantified galactosaminoglycans (GAAGs), oligomeric cartilage matrix protein (COMP), and human cartilage glycoprotein 39 (YKL-40) in blood obtained from juvenile idiopathic arthritis (JIA) before and during 2-year treatment with etanercept (ETA), as potential biomarkers of cartilage extracellular matrix (ECM) dysfunction and indicators of efficacy of biologic therapy. We also evaluated the relationship of the mentioned markers with the factors that regulate their metabolism, disintegrin and thrombospondin motif metalloproteinases 4 (ADAMTS4), ADAMTS5, and platelet-derived growth factor BB (PDGF-BB). Methods: We studied 38 children diagnosed with JIA and 45 healthy children. We quantified GAAGs by assessing the concentration of unsaturated disaccharide units formed by digestion of isolated glycosaminoglycans with chondroitinase ABC, while COMP, YKL-40, and PDGF-BB were quantified using immunoenzymatic methods. Results: Compared to the control group, GAAGs and COMP levels were significantly lower, while YKL-40 levels were higher in the blood of patients with aggressive JIA, qualified for ETA treatment. ETA therapy leading to clinical improvement simultaneously promoted normalization of COMP and YKL-40 levels, but not GAAGs. After 24 months of taking ETA, glycan levels were still significantly lower, relative to controls. GAAGs, COMP, and YKL-40 levels were significantly influenced by ADAMTS4, ADAMTS5, and PDGF-BB levels both before and during ETA treatment. Conclusions: The dynamics of changes in marker concentrations during treatment seem to indicate that measurement of COMP and YKL-40 levels can be used to assess the chondroprotective biological efficacy of therapy. In contrast, changes in GAAGs concentrations reflect systemic extracellular matrix transformations in the course of JIA.
Keywords	juvenile idiopathic arthritis ; etanercept ; extracellular matrix turnover markers ; galactosaminoglycans ; oligomeric cartilage matrix protein ; human cartilage glycoprotein 39 ; Medicine ; R
Subject code	610 ; 616
Language	English
Publishing date	2022-08-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Significant Remodeling Affects the Circulating Glycosaminoglycan Profile in Adult Patients with both Severe and Mild Forms of Acute Pancreatitis.

Koźma, Ewa M / Kuźnik-Trocha, Kornelia / Winsz-Szczotka, Katarzyna / Wisowski, Grzegorz / Olczyk, Paweł / Komosińska-Vassev, Katarzyna / Kasperczyk, Mariusz / Olczyk, Krystyna

Journal of clinical medicine

2020 Volume 9, Issue 5

Abstract: Acute pancreatitis (AP) manifests itself either as a mild, self-limiting inflammation or a severe, systemic inflammatory process that is associated with various complications and a high mortality rate. It is unknown whether these two forms of the disease ...

Abstract	Acute pancreatitis (AP) manifests itself either as a mild, self-limiting inflammation or a severe, systemic inflammatory process that is associated with various complications and a high mortality rate. It is unknown whether these two forms of the disease can differ in the profile of circulating glycosaminoglycans, which are molecules with huge biological reactivity due to a high density of negative electric charge. Plasma glycosaminoglycans were characterized/quantified in 23 healthy controls, 32 patients with mild AP, and 15 individuals with severe disease using electrophoresis with enzymatic identification (chondroitin sulfate and heparan sulfate) or an ELISA-based test (hyaluronan). Moreover, the correlations between the glycosaminoglycan levels and clinical parameters were evaluated. Both forms of AP showed similar remodeling of the plasma profile of the sulfated glycosaminoglycans. In contrast, only in the patients with mild AP was the level of circulating hyaluronan significantly decreased as compared to the healthy controls. Both forms of AP are associated with systemic changes in the metabolism of glycosaminoglycans. However, the alterations in hyaluronan metabolism may contribute to the disease evolution. The circulating hyaluronan may have some clinical value to predict the severity of AP and to evaluate the clinical status of patients with severe AP.
Language	English
Publishing date	2020-05-01
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm9051308
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Article: The dual role of the glycosaminoglycan chondroitin‐6‐sulfate in the development, progression and metastasis of cancer

Pudełko, Adam / Wisowski, Grzegorz / Olczyk, Krystyna / Koźma, Ewa Maria

FEBS journal. 2019 May, v. 286, no. 10

2019

Abstract	The remarkable structural heterogeneity of chondroitin sulfate (CS) and dermatan sulfate (DS) generates biological information that can be unique to each of these glycosaminoglycans (GAGs), and changes in their composition are translated into alterations in the binding profiles of these molecules. CS/DS can bind to various cytokines and growth factors, cell surface receptors, adhesion molecules, enzymes and fibrillar glycoproteins of the extracellular matrix, thereby influencing both cell behavior and the biomechanical and biochemical properties of the matrix. In this review, we summarize the current knowledge concerning CS/DS metabolism in the human cancer stroma. The remodeling of the GAG profile in the tumor niche is manifested as a substantial increase in the CS content and a gradual decrease in the proportion between DS and CS. Furthermore, the composition of CS and DS is also affected, which results in a substantial increase in the 6‐O‐sulfated and/or unsulfated disaccharide content, which is concomitant with a decrease in the 4‐O‐sulfation level. Here, we discuss the possible impact of alterations in the CS/DS sulfation pattern on the binding capacity and specificity of these GAGs. Moreover, we propose potential consequences of the stromal accumulation of chondroitin‐6‐sulfate for the progression and metastasis of cancer.
Keywords	adhesion ; binding capacity ; biomechanics ; chondroitin sulfate ; cytokines ; dermatan sulfate ; enzymes ; extracellular matrix ; glycoproteins ; growth factors ; humans ; metabolism ; metastasis ; neoplasms ; receptors
Language	English
Dates of publication	2019-05
Size	p. 1815-1837.
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	REVIEW
ZDB-ID	2173655-8
ISSN	1742-4658 ; 1742-464X
ISSN (online)	1742-4658
ISSN	1742-464X
DOI	10.1111/febs.14748
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Dermatan sulfate is a player in the transglutaminase 2 interaction network.

Wisowski, Grzegorz / Koźma, Ewa M / Bielecki, Tomasz / Pudełko, Adam / Olczyk, Krystyna

PloS one

2017 Volume 12, Issue 2, Page(s) e0172263

Abstract: Transglutaminase 2 (TG2) is a multifunctional protein that is primarily engaged in cell adhesion/signaling or shows Ca2+-dependent transglutaminase activity in the extracellular space of tissues. This latter action leads to the cross-linking of the ... ...

Abstract	Transglutaminase 2 (TG2) is a multifunctional protein that is primarily engaged in cell adhesion/signaling or shows Ca2+-dependent transglutaminase activity in the extracellular space of tissues. This latter action leads to the cross-linking of the extracellular matrix (ECM) proteins. The enhanced extracellular expression of TG2 is associated with processes such as wound healing, fibrosis or vascular remodeling that are also characterized by a high deposition of dermatan sulfate (DS) proteoglycans in the ECM. However, it is unknown whether DS may bind to TG2 or affect its function. Using the plasmon surface resonance method, we showed that DS chains, especially those of biglycan, are good binding partners for TG2. The interaction has some requirements as to the DS structure. The competitive effect of heparin on DS binding to TG2 suggests that both glycosaminoglycans occupy the same binding site(s) on the protein molecule. An occurrence of the DS-TG2 interaction was confirmed by the co-immunoprecipitation of this protein with native decorin that is a DS-bearing proteoglycan rather than with the decorin core protein. Moreover, in vivo DS is responsible for both TG2 binding and the regulation of the location of this protein in the ECM as can be suggested from an increased extraction of TG2 from the human fascia only when an enzymatic degradation of the tissue DS was conducted in the presence of the anti-collagen type I antiserum. In addition, DS with a low affinity for TG2 exerted an inhibitory effect on the protein transamidating activity most probably via the control of the accessibility of a substrate. Our data show that DS can affect several aspects of TG2 biology in both physiological and pathological conditions.
MeSH term(s)	Animals ; Cell Line ; Chromatography, High Pressure Liquid ; Dermatan Sulfate/chemistry ; Dermatan Sulfate/metabolism ; GTP-Binding Proteins/chemistry ; GTP-Binding Proteins/metabolism ; Humans ; Immunoprecipitation ; Protein Binding ; Surface Plasmon Resonance ; Swine ; Transglutaminases/chemistry ; Transglutaminases/metabolism
Chemical Substances	Dermatan Sulfate (24967-94-0) ; transglutaminase 2 (EC 2.3.2.-) ; Transglutaminases (EC 2.3.2.13) ; GTP-Binding Proteins (EC 3.6.1.-)
Language	English
Publishing date	2017-02-15
Publishing country	United States
Document type	Journal Article
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0172263
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Significant Remodeling Affects the Circulating Glycosaminoglycan Profile in Adult Patients with both Severe and Mild Forms of Acute Pancreatitis

Ewa M. Koźma / Kornelia Kuźnik-Trocha / Katarzyna Winsz-Szczotka / Grzegorz Wisowski / Paweł Olczyk / Katarzyna Komosińska-Vassev / Mariusz Kasperczyk / Krystyna Olczyk

Journal of Clinical Medicine, Vol 9, Iss 1308, p

2020 Volume 1308

Abstract	Acute pancreatitis (AP) manifests itself either as a mild, self-limiting inflammation or a severe, systemic inflammatory process that is associated with various complications and a high mortality rate. It is unknown whether these two forms of the disease can differ in the profile of circulating glycosaminoglycans, which are molecules with huge biological reactivity due to a high density of negative electric charge. Plasma glycosaminoglycans were characterized/quantified in 23 healthy controls, 32 patients with mild AP, and 15 individuals with severe disease using electrophoresis with enzymatic identification (chondroitin sulfate and heparan sulfate) or an ELISA-based test (hyaluronan). Moreover, the correlations between the glycosaminoglycan levels and clinical parameters were evaluated. Both forms of AP showed similar remodeling of the plasma profile of the sulfated glycosaminoglycans. In contrast, only in the patients with mild AP was the level of circulating hyaluronan significantly decreased as compared to the healthy controls. Both forms of AP are associated with systemic changes in the metabolism of glycosaminoglycans. However, the alterations in hyaluronan metabolism may contribute to the disease evolution. The circulating hyaluronan may have some clinical value to predict the severity of AP and to evaluate the clinical status of patients with severe AP.
Keywords	acute pancreatitis ; plasma glycosaminoglycans ; chondroitin sulfate ; heparan sulfate ; hyaluronan ; Medicine ; R
Subject code	610
Language	English
Publishing date	2020-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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