Chondroitin Sulfate as a Key Molecule in the Development of Atherosclerosis and Cancer Progression

• Published in: Advances in Pharmacology Vol. 53; pp. 281 - 295
• Main Authors: Theocharis, A.D., Tsolakis, I., Tzanakakis, G.N., Karamanos, Nikos K.
• Format: Book Chapter Journal Article
• Language: English
• Published: United States Elsevier Inc 2006
• Subjects: Animals; Antineoplastic Agents - therapeutic use; Aorta - physiology; Atherosclerosis - etiology; Biomechanical Phenomena; Chondroitin Sulfate Proteoglycans - chemistry; Chondroitin Sulfate Proteoglycans - physiology; Chondroitin Sulfates - physiology; Chondroitin Sulfates - therapeutic use; Cytokines - physiology; Disease Progression; Epidermal Growth Factor - metabolism; Extracellular Matrix - metabolism; Heparin-binding EGF-like Growth Factor; Humans; Intercellular Signaling Peptides and Proteins; Lipoproteins, LDL - metabolism; Neoplasms - etiology; Signal Transduction; Versicans - physiology
• ISBN: 9780120329557; 0120329557
• ISSN: 1054-3589; 1557-8925
• DOI: 10.1016/S1054-3589(05)53013-8

This chapter discusses the molecular involvement of CS in the progression of two main human diseases: cancer and atherosclerosis. Chondroitin sulfate (CS) is a glycosaminoglycan (GAG) composed of repeating disaccharides of glucuronic acid and N‐acetyl‐galactosamine, which are variously substituted by sulfate groups. It is covalently attached on several core proteins creating a variety of proteoglycans (PGs) found in the extracellular matrix (ECM) and cell membrane, but also intracellularly. Chondroitin sulfate interacts with a wide variety of key molecules, such as growth factors, cytokines, chemokines, adhesion molecules and lipoproteins via specific saccharide domains within the chain. These interactions regulate several biological processes and cell behavior. Several diseases are often associated with a biosynthetic imbalance of chondroitin sulfate proteoglycans (CSPGs). CSPGs are markedly increased in early atherosclerotic lesions, playing important roles in lipid retention, modification, and finally accumulation. In addition, CSPGs participate in inflammatory process associated with atherosclerosis and influence arterial smooth muscle cell behavior. They also directly affect elastogenesis and proper formation of the extracellular matrix. CSPGs are markedly accumulated also in tumor stroma and its deposition is often correlated to poor prognosis of the disease.