Hyaluronan promotes the malignant phenotype

Abstract

Hyaluronan is a high-molecular-weight, negatively charged polysaccharide with unusual physical and interactive properties. Hyaluronan is localized in the extracellular matrix, at the cell surface, and inside cells. Its tissue distribution is ubiquitous, but it is particularly concentrated in pericellular matrices surrounding proliferating and migrating cells. Hyaluronan contributes to cell behavior in at least three ways. Its unique physical properties influence the biomechanical properties of extracellular and pericellular matrices; it is a template for assembly of other pericellular macromolecules; and it interacts directly with cell surface receptors that transduce intracellular signals. Experimental studies in animal models have documented a crucial role for hyaluronan in tumor growth and metastasis. Cellular manipulations have shown that hyaluronan promotes anchorage-independent growth and invasiveness, hallmarks of the malignant phenotype.