Heparanase is the unique and specific functional
endoglycosidase capable of cleaving
heparan sulfate (HS) chains. It exerts its enzymatic activity catalyzing the cleavage of the β (1,4)-glycosidic bond between
glucuronic acid and
glucosamine residue. HS cleavage results in remodelling of the extracellular matrix as well as in regulating the release of many HS-linked molecules such as
growth factors,
cytokines and
enzymes involved in
inflammation, wound healing and tumour invasion. A pro-metastatic and pro-angiogenic role for this
enzyme has been widely demonstrated in many primary human tumours since high levels of
heparanase correlate with lymph node and distant
metastasis, elevated micro vessel density and reduced survival of
cancer patients. Recently, data have been reported that
heparanase regulates
heparan sulfate proteoglycan syndecan-1 and promotes its shedding from the cell surface. Shed
syndecan-1 in turn controls tumour growth,
metastasis and neo-angiogenesis mainly by promoting
growth-factor signaling in the tumour milieu. Considering that, once inactivated, there are no other molecules capable of performing the same function, it is evident how this
enzyme may be an effective and attractive
drug target. Several
heparanase inhibitors have been developed and some of them have undergone clinical trials showing efficacy against tumours. In this mini-review we will discuss current knowledge of
heparanase involvement in
cancer as well as its targeted inhibition as a promising therapeutic option in tumour treatment.