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The dual role of the glycosaminoglycan chondroitin‐6‐sulfate in the development, progression and metastasis of cancer

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. C...

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Autores principales: Pudełko, Adam, Wisowski, Grzegorz, Olczyk, Krystyna, Koźma, Ewa Maria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6850286/
https://www.ncbi.nlm.nih.gov/pubmed/30637950
http://dx.doi.org/10.1111/febs.14748
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author Pudełko, Adam
Wisowski, Grzegorz
Olczyk, Krystyna
Koźma, Ewa Maria
author_facet Pudełko, Adam
Wisowski, Grzegorz
Olczyk, Krystyna
Koźma, Ewa Maria
author_sort Pudełko, Adam
collection PubMed
description 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.
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spelling pubmed-68502862019-11-18 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 J Review Article 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. John Wiley and Sons Inc. 2019-02-05 2019-05 /pmc/articles/PMC6850286/ /pubmed/30637950 http://dx.doi.org/10.1111/febs.14748 Text en © 2019 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Pudełko, Adam
Wisowski, Grzegorz
Olczyk, Krystyna
Koźma, Ewa Maria
The dual role of the glycosaminoglycan chondroitin‐6‐sulfate in the development, progression and metastasis of cancer
title The dual role of the glycosaminoglycan chondroitin‐6‐sulfate in the development, progression and metastasis of cancer
title_full The dual role of the glycosaminoglycan chondroitin‐6‐sulfate in the development, progression and metastasis of cancer
title_fullStr The dual role of the glycosaminoglycan chondroitin‐6‐sulfate in the development, progression and metastasis of cancer
title_full_unstemmed The dual role of the glycosaminoglycan chondroitin‐6‐sulfate in the development, progression and metastasis of cancer
title_short The dual role of the glycosaminoglycan chondroitin‐6‐sulfate in the development, progression and metastasis of cancer
title_sort dual role of the glycosaminoglycan chondroitin‐6‐sulfate in the development, progression and metastasis of cancer
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6850286/
https://www.ncbi.nlm.nih.gov/pubmed/30637950
http://dx.doi.org/10.1111/febs.14748
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