Proteoglycans in normal physiology and carcinogenesis

Abstract

Malignant transformation of any cell is associated with numerous physiological and morphological disorders at both genomic and protein levels, a variety of macromolecules being involved in. However, the tumour development and metastasis depends on not only the molecular characteristics of the tumour cell but also its interaction with the surrounding extracellular matrix (ECM), which is an important and necessary part of any tissue. An important role in this process belongs to the complex protein-carbohydrate molecules – proteoglycans (PG), which are one of the main component of ECM and cell surface of any tissue and are tightly involved in cell-cell and cell-matrix interactions and signaling. During carcinogenesis, significant changes in the PG structure and composition occur both at the surface of tumour cells and surrounding ECM, resulting in the transformation of normal ECM into a tumour microenvironment and deterioration of cell-cell and cell-matrix communication. Further, the tumorigenic niche contributes to active proliferation of the cancer cells, tumour development and metastasis. At present, many key PG are identified as possible diagnostic and prognostic molecular markers and target molecules for the creation of new antitumor drugs.The review describes the main PG types, their structure, localisation, functional role in normal cell and tissue physiology and participation in molecular mechanisms of carcinogenesis.

Keywords

• proteoglycan
• glycosaminoglycan
• heparansulfate
• chondroitinsulfate
• extracellular matrix
• cell-cell and cell-matrix interactions
• carcinogenesis
• tumour microenvironment
• metastasis