Heparan sulphate
proteoglycans (HSPGs) consist of a core
protein and several heparan sulphate (HS) side chains covalently linked. HS also binds a great deal of
growth factors,
chemokines,
cytokines and
enzymes to the extracellular matrix and cell surface.
Heparanase can specially cleave HS side chains from HSPGs. There are a lot of conflicting reports about the role of
heparanase in
hepatocellular carcinoma (HCC).
Heparanase is involved in
hepatitis B virus infection and hepatitis C virus
infection, the activation of signal pathways,
metastasis and apoptosis of HCC.
Heparanase is synthesized as an inactive precursor within late endosomes and lysosomes. Then
heparanase undergoes proteolytic cleavage to form an active
enzyme in lysosomes. Active
heparanase translocates to the nucleus, cell surface or extracellular matrix. Different locations of
heparanase may exert different activities on
tumor progression. Furthermore, enzymatic activities and non-enzymatic activities of
heparanase may play different roles during HCC development. The expression level of
heparanase may also contribute to the discrepant effects of
heparanase. Growth promoting as well as growth inhibiting sequences are contained within the
tumor cell surface
heparan sulfate. Degrading different HSPGs by
heparanase may play different roles in HCC. Systemic studies examining the processing, expression, localization and function of
heparanase should shed a light on the role of
heparanase in HCC.