Heparanase as a molecular target of cancer chemotherapy

Cancer Sci. 2004 Jul;95(7):553-8. doi: 10.1111/j.1349-7006.2004.tb02485.x.

Abstract

Cancer cells require the ability to degrade the extracellular matrix (ECM) in order to turn into invasive and metastatic cancer cells. Many proteases and glycosidases are essential in the process of dissolving the components of the ECM. An endo-beta-D-glucuronidase, heparanase, is capable of specifically degrading one of the ECM components, heparan sulfate, and this activity is associated with the metastatic potential of tumor cells. Since heparanase mRNA is overexpressed in many human tumors (e.g., hepatomas, head and neck tumors, and esophageal carcinomas), the mechanisms regulating the activity of heparanase should be clarified; considering the possible role of heparanase in cancer, the development of heparanase inhibitors would appear to be advantageous. This review will focus on recent findings that have contributed to the characterization of heparanase and to the elucidation of the transcriptional regulation of heparanase mRNA expression, as well as the development of heparanase inhibitors.

Publication types

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

MeSH terms

  • Enzyme Inhibitors / pharmacology
  • Extracellular Matrix / metabolism*
  • Glucuronidase / antagonists & inhibitors*
  • Glucuronidase / biosynthesis
  • Glucuronidase / pharmacology*
  • Humans
  • Neoplasms / enzymology*
  • Neoplasms / physiopathology
  • RNA / biosynthesis

Substances

  • Enzyme Inhibitors
  • RNA
  • heparanase
  • Glucuronidase