Chitinase 3-Like-1 (CHI3L1): A Putative Disease Marker at the Interface of Proteomics and Glycomics

Abstract

Chitinase 3-Like-1 (CHI3L1) is a secreted 40 kDa glycoprotein that is upregulated in a number of human cancers and in non-neoplastic disease states characterized by chronic inflammation and tissue remodeling. Increased serum levels of CHI3L1 parallel disease severity, poorer prognosis, and shorter survival in many human neoplasias, including cancers of the breast, colon, prostate, ovaries, brain, thyroid, lung, and liver. Increased serum CHI3L1 also correlates with disease severity in rheumatoid arthritis, osteoarthritis, liver fibrosis, inflammatory bowel disease, and bacterial septicemia. CHI3L1 is a rheumatoid arthritis (RA) autoantigen, and MHC complexes containing specific CHI3L1 peptides have been found in RA patients; however, intranasal introduction of these same CHI3L1 peptides can induce tolerance towards them. CHI3L1 is a nonhydrolytic member of the human chitinase family that binds chitin tightly and heparin at lower affinity. Interactions with type I collagen, CHI3L1's only known protein-binding partner, helps regulate collagen fibril formation. The principal sources of CHI3L1 are activated macrophages and chondrocytes, neutrophils, and some tissue and tumor cells. CHI3L1 can act as a fibroblast mitogen and can activate several signaling pathways, however, no cell surface-binding partner for CHI3L1 has been identified. The ability of CHI3L1 to bind both proteins and carbohydrates allows potential interactions with a variety of cell-surface and extracellular-matrix proteins, proteoglycans, and polysaccharides, and thus CHI3L1 can interface between proteomics and glycomics.

Keywords:

• arthritis
• cartilage
• chitinase
• chondrocyte
• glycoprotein
• hcGP-39
• inflammation
• macrophage
• neoplasia
• neutrophil
• tolerance
• YKL-40