Published online Jan 7, 2016. doi: 10.3748/wjg.v22.i1.379
Peer-review started: May 31, 2015
First decision: July 14, 2015
Revised: September 14, 2015
Accepted: November 9, 2015
Article in press: November 9, 2015
Published online: January 7, 2016
Proteoglycans are a group of molecules that contain at least one glycosaminoglycan chain, such as a heparan, dermatan, chondroitin, or keratan sulfate, covalently attached to the protein core. These molecules are categorized based on their structure, localization, and function, and can be found in the extracellular matrix, on the cell surface, and in the cytoplasm. Cell-surface heparan sulfate proteoglycans, such as syndecans, are the primary type present in healthy liver tissue. However, deterioration of the liver results in overproduction of other proteoglycan types. The purpose of this article is to provide a current summary of the most relevant data implicating proteoglycans in the development and progression of human and experimental liver cancer. A review of our work and other studies in the literature indicate that deterioration of liver function is accompanied by an increase in the amount of chondroitin sulfate proteoglycans. The alteration of proteoglycan composition interferes with the physiologic function of the liver on several levels. This article details and discusses the roles of syndecan-1, glypicans, agrin, perlecan, collagen XVIII/endostatin, endocan, serglycin, decorin, biglycan, asporin, fibromodulin, lumican, and versican in liver function. Specifically, glypicans, agrin, and versican play significant roles in the development of liver cancer. Conversely, the presence of decorin could potentially provide protective effects.
Core tip: Proteoglycans are molecules that contain at least one glycosaminoglycan chain and are primarily found on the cell surface and in the extracellular matrix, where they serve as structural components. In addition, their glycosaminoglycan chains interact with numerous regulatory molecules, thus potentially influencing a myriad of cellular processes, including those linked with cancer development. For example, they can support or inhibit signaling of growth factors, cytokines, and hormones. This article reviews current data demonstrating the versatile role of proteoglycans in the development, maintenance, and progression of liver cancer.