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.
Highlights
The local microenvironment of living cells, referred to as the tissue stroma or niche, consists of host cells and an extracellular matrix (ECM) that surrounds them
Biglycan and other commonly spread matrix PGs that are substituted with chondroitin sulfate (CS) or dermatan sulfate (DS), such as decorin or versican, affect cellular function both directly and indirectly through an impact on the formation of the ECM architecture as well as through binding to and influencing the activity of various functional molecules [10,11]
The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies
Summary
The dual role of the glycosaminoglycan chondroitin-6sulfate 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. 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. We discuss the possible impact of alterations in the CS/DS sulfation pattern on the binding capacity and specificity of these GAGs. we propose potential consequences of the stromal accumulation of chondroitin-6-sulfate for the progression and metastasis of cancer
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