Proteoglycans and the Intercellular Tumor Matrix

Abstract

The intercellular matrix is a highly organized, dynamic system that dictates the overall shape and structure of organs. The spatial and chemical signals which are present in the extracellular matrix modulate the phenotypic expression of epithelial and mesenchymal cells. In turn, these cells regulate the chemistry and structural organization of the extracellular matrix. This active interplay between cells and their products leads to the formation of a highly complex environment in which normal and neoplastic cells can thrive and proliferate. Proteoglycans are suitable candidates for mediating this constant exchange of information. For instance, they influence the diffusion of molecules across tissues, the migration of cells along defined pathways, the surface properties of cells, and the structure of biological filters. These effects are primarily mediated by the polyanionic nature of the proteoglycan, by their expanded configuration in tissues and body fluids, and by their ability to interact with a variety of important matrix macromolecules. They are indeed constituents of both the stromal matrix and the cell surface (Fig. 1), and their biosynthesis, secretion and metabolism are highly regulated by intrinsic and extrinsic signals. These molecules are composed of a protein backbone to which a number of glycosaminoglycan chains and oligosaccharides are covalently attached, much like the branches to a tree. The proteoglycan-rich intercellular matrix can thus be conceived as a microcosmic forest, the properties of which depend primarily on the number, size and structure of the various glycosaminoglycan chains and their complex intermolecular affiliations.