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The dual role of the glycosaminoglycan chondroitin‐6‐sulfate in the development, progression and metastasis of cancer
Author(s) -
Pudełko Adam,
Wisowski Grzegorz,
Olczyk Krystyna,
Koźma Ewa Maria
Publication year - 2019
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14748
Subject(s) - sulfation , dermatan sulfate , glycosaminoglycan , extracellular matrix , chondroitin sulfate , chemistry , chondroitin , biochemistry , heparan sulfate , stromal cell , metastasis , cancer cell , cell adhesion , microbiology and biotechnology , cell , cancer , cancer research , biology , genetics
The remarkable structural heterogeneity of chondroitin sulfate ( CS ) and dermatan sulfate ( DS ) generates biological information that can be unique to each of these glycosaminoglycans ( GAG s), 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 GAG s. Moreover, we propose potential consequences of the stromal accumulation of chondroitin‐6‐sulfate for the progression and metastasis of cancer.