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.
Keywords: Angiogenesis, cancer, extracellular matrix, heparanase, heparanase inhibitors, heparan sulfate, metastasis.
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