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

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.

Transcriptome sequencing analysis of mono‑ADP‑ribosylation in colorectal cancer cells

“…Chondroitin sulfate/dermatan sulfate proteoglycans exert their functions by interacting with specific proteins, such as growth factors, matrix proteins and cell surface receptors, and they serve an important role in cancer (28). Dermatan sulfate epimerase catalyzes the conversion of chondroitin sulfate to dermatan sulfate, and is considered an important mediator of the development of malignant characteristics in hepatocellular carcinoma (51). The metabolism of chondroitin sulfate/dermatan sulfate in tumor stroma is strongly altered.…”

Distribution and Function of Glycosaminoglycans and Proteoglycans in the Development, Homeostasis and Pathology of the Ocular Surface

“…In normal human corneas there are 8 μg of CS/DS per mg dry weight with ∼40 disaccharides per chain, which decreases to ∼15 disaccharides in corneas affected by macular corneal dystrophies ( Plaas et al, 2001 ). CSPGs are important ECM components with diverse functions in tissues, such as regulating cell adhesion, cell growth, neuronal plasticity, neuronal regeneration and cell migration, and form the bulk of the majority of connective tissues ( Coulson-Thomas et al, 2008 , 2016 ; Silver et al, 2013 ; Silver and Silver, 2014 ; Smith et al, 2015 ; Gesteira et al, 2016 ; Pai et al, 2018 ; Pudełko et al, 2019 ).…”

Epigenetic mechanism of carbohydrate sulfotransferase 3 (CHST3) downregulation in the aging brain

“…The increased ratio of C4S/C6S on the GAG's that are present on PNN forming core protein aggrecan attracted the most attention as a potential mechanism behind the plasticity-restraining function of ECM. Moreover, the increase in the ratio is largely attributed to the decrease in C6S GAG's (Foscarin et al, 2017;Pudelko et al, 2019). Here, we demonstrate that CHST3 expression is strongly downregulated both in the cortex and the hippocampus of 24-26M mouse brain compared to the 2-3M brain.…”