Heparanase

• OMIM: 604 724
• UniProt: Q9Y251
• MGI: 1343124

Heparanase (synonyms: heparan sulfate endoglycosidase, Endo- β -D -glucuronidase ) is a body formed from the enzyme, an endoglycosidase that specifically cleaves heparan sulfate chains of the cell surface and basement membrane heparan sulfate proteoglycans and in numerous important biological processes such as, for as tumor invasion and metastasis is involved.

Synthesis

Heparanase is first formed as an inactive pro-enzyme of approximately 65 kDa. For this proenzyme a 6 kDa fragment is proteolytically excised and the two resulting 8 kDa and 50 kDa fragments form the active heterodimer. Heparanase cleaves heparan sulfate and heparin only a few defined interfaces of the polysaccharide chain.

Biological significance and inhibition

Heparan sulfate proteoglycans (HS -PG) are a group of complex macromolecules, which are expressed on the cell surface of most cells, but also in particular in all basement membranes and in the extracellular matrix and, among other important roles in the control of cell proliferation and differentiation have (for example as co-receptors of cytokines and growth factors). In addition, HS -PG important constituents of the basement membrane and not only control the mass transfer (such as in the glomerular basement membrane ), but also cell migration.

In the context of inflammatory and immune reactions must inflammatory and immune cells, ie mainly neutrophils, monocytes and lymphocytes from the blood vessels migrate into the inflamed area and this overcome the basement membranes. For the basement membrane passage it is necessary to degrade the basement membrane locally, especially the heparan sulfate chains of HS -PG. Accordingly, the enzyme heparanase on a number of cell types, in particular leukocytes, platelets but is also expressed in many tumor cells.

By inhibiting heparanase can therefore be not only inhibit inflammatory reactions but also the invasion and metastasis of tumors. The high expression of heparanase by tumor cells is a prognostic marker, for example, in pancreatic carcinoma. The development of suitable heparanase inhibitors forms, especially because in humans, only one gene for heparanase exists, a new interesting approach in tumor therapy.

The enzyme heparanase bound to heparan sulfate cytokines and growth factors may also on cell surfaces, in the basement membrane but are released (eg, bFGF) and thus but to control processes such as angiogenesis and wound healing and repair processes, particularly in the extracellular matrix.

Proof

For the measurement of heparanase activity, an enzyme immunoassay has recently become available.

• Glycosidase