Heparanase: a target for therapy of brain invasive tumors?

Mechanisms responsible for the progression of malignant melanoma to highly aggressive brain-metastatic disease remain largely unknown. Brain neurotrophins can modulate the brain invasion of melanoma cells and the activity of an enzyme called heparanase. Heparanase is an endo-beta-D-glucuronidase that degrades the heparan sulfate chains of heparan sulfate proteoglycans, essential and ubiquitous macromolecules associated with the cell surface and the extracellular matrix of a wide range of cells and tissues. Human heparanase has been recently cloned as a single gene family and found to be a potential target for anticancer drugs because of its critical roles in angiogenic and invasive processes. The potential relevance of heparanase, as a cellular switch from noninvasive to the invasive phenotype and novel therapeutic target for invasive brain tumors, is introduced.