Proteoglycans in liver cancer

World J Gastroenterol. 2016 Jan 7;22(1):379-93. doi: 10.3748/wjg.v22.i1.379.

Abstract

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.

Keywords: Cancer; Cell regulation; Heparan sulfate; Liver; Proteoglycans.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Agrin / metabolism
  • Animals
  • Carcinoma, Hepatocellular / etiology
  • Carcinoma, Hepatocellular / metabolism
  • Glycosaminoglycans / chemistry
  • Glycosaminoglycans / metabolism
  • Glypicans / metabolism
  • Heparan Sulfate Proteoglycans / chemistry
  • Heparan Sulfate Proteoglycans / metabolism
  • Humans
  • Liver Neoplasms / etiology
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms, Experimental / etiology
  • Liver Neoplasms, Experimental / metabolism
  • Proteoglycans / chemistry
  • Proteoglycans / metabolism*
  • Syndecan-1 / metabolism
  • Versicans / metabolism

Substances

  • Agrin
  • Glycosaminoglycans
  • Glypicans
  • Heparan Sulfate Proteoglycans
  • Proteoglycans
  • SDC1 protein, human
  • Syndecan-1
  • VCAN protein, human
  • Versicans
  • perlecan