The proteoglycan versican: an important regulator of cell locomotion in development and disease

Abstract

One of the major keys to understanding tissue reorganization during embryological development and pathophysiology will be to decipher the mechanisms that regulate cell locomotion. This review focuses on what is known about versican, a large extracellular proteoglycan intimately involved in cellular relocation and tissue reorganization during normal processes and pathological states, including cancer metastasis. A member of the lectican family, versican plays diverse roles in cell adhesion, proliferation, migration and angiogenesis. These wide ranging functions have been attributed to the N-(G1) and C-(G3) terminal globular domains and the central glycosaminoglycan-binding region of versican, which collectively interact with a large number of extracellular matrix and cell surface structural components. Consequently, the diverse roles of versican may depend on the level of specific isoforms and/or levels of G1 and G3 domains which can be generated as a result of processing by specific proteases. Little is known about versican catabolism and whether its proteolytic fragments have altered biological activity compared to the intact molecule in physiological and disease processes. Studies over the last ten years have confirmed a significant role for versican in regulating cell locomotion in normal development and disease.