PROTEOGLYCANS IN NORMAL PHYSIOLOGY AND CARCINOGENESIS

Аннотация

The emergence and development of malignant tumors is associated with numerous disturbances in the physiology of the cell at both the genomic and protein levels and affects many macromolecules involved in various aspects of its vital activity. However, the growth of a malignant tumor and its metastasis are determined not only by the molecular characteristics of thetumorcell itself, but also byits interaction with thesurrounding extracellular matrix (ECM) – an important and necessary part of any tissue. A huge role in this is played by complex protein- carbohydrate molecules of proteoglycans (PG), which are one of the main components of the ECM and are present on the surface of almost all cells, largely determining intercellular interactions and interactions ofcells with theECM. Kеywоrds:proteoglycan, heparan sulfate, glycosaminoglycan, extracellular matrix, chondroitin sulfate, intercellularinteractions. INTRОDUСTIОN At present, despite intensive research, the causes of malignant tumors and the molecular mechanisms of carcinogenesis remain insufficiently studied. It is known that this process is associated with the functioning of many signaling pathways involving various molecules, the composition, structure and expression of which undergo significant changes in the process of malignant transformation of cells and tissues, which largely determines the initiation and development of the pathological process. Along with the actively studied macromolecules of nucleic acids, proteins, polysaccharides and lipids, protein-carbohydrate molecules called proteoglycans (PG) also play a significant role in the physiology of cells and tissues and their malignant transformation. MАTЕRIАLS АNDMЕTHОDS PGs are complex protein-carbohydrate molecules consisting of a core protein and carbohydrate chains of glycosaminoglycans (GAGs) covalently attached to it [1]. They represent a separate class of biological macromolecules that differ fundamentally from glycoproteins precisely in the structure of their carbohydrate chains. Polysaccharide chains of GAGs are linear polymers consisting of repeating disaccharide subunits, each of which includes hexosamine (D- glucosamine or D-galactosamine) and uronic acid (D-glucuronic or L-iduronic). Each disaccharide can undergo selective modification at various positions (sulfation at the 2-, 3- and 6-O-positions and acetylation/sulfation at the N-position), which leads to a high anionic charge of the disaccharides themselves and the GAG ​ ​ carbohydrate chain formed from them and the PGmolecule as awhole. RЕSULTSАNDDISСUSSIОN GS is one of themain classes of GAGs. Its carbohydrate chains consist of N-acetylated or N-sulfated D-glucosamine (GlcNAc), which is linked to D-glucuronic (GlcA) or L-iduronic acid (IdoUA) [2]. A special type of GS is heparin, which is characterized by a high degree of sulfation of iduronic acid (at carbon 2 (IdoA2S)) and N-sulfated glucosamine (at position 6 (GlcNS6S)). The degree of sulfation of heparin is much higher than GS, which makes heparin the most charged of all known biomolecules, which is a widely used pharmaceutical anticoagulant. page237 INTERNATIONAL JOURNAL OF ARTIFICIAL INTELLIGENCE ISSN:2692-5206,ImpactFactor:12,23 AmericanAcademicpublishers,volume05,issue03,2025 Journal: https://www.academicpublishers.org/journals/index.php/ijai CS contain alternating residues of glucuronic acid (GlcUA) and N-acetylgalactosamine (GalNAc). They vary significantly in chain length and molecular weight: their weight fluctuates in the range from 5 to 70 kDa, even when isolated from the same source [3]. Like GS, CS can be N- and/or O-sulfated or acetylated at the 2, 3, 4 and/or 6 positions and are highly anionic molecules with a heterogeneous structure, and the pattern of their sulfation directly affects their biological functions. DS is completely identical to the CS molecule in its composition, but contains a stereoisomer of glucuronic acid (D-GlcUA) – iduronic acid (L-IdoUA). It is the presence of the L-IdoUA stereoisomer that allows such a molecule to be called DS and not CS. Glucuronic (GlcA) or iduronic (IdoA) acid in DS can be partially sulfated at the C2 position, and N-acetylgalactosamine(GalNAc) at theC4or C6position [4]. Structureof keratan sulfates The main disaccharide of keratan sulfates consists of N-acetylglucosamine (GlcNAc) and galactose, both of which can be sulfated at the C6 position. Therefore, keratan sulfate is the only type of GAG that lacks a carboxyl group [2]. The molecular weight of keratan sulfate ranges from 5 to 25 kDa and strongly depends on the tissue origin. The highest concentration of keratan sulfate is found in the cornea. Keratan sulfate is a structural component of several PGs – aggrecan, contained in cartilage, and small leucine-rich PGs (lumican, keratocan, fibromodulin). In addition to the extracellular matrix (ECM), keratan sulfates are also found intracellularly in eosinophil-specific granules and as part of cellular transmembrane