Heparanase function in tumour metastasis and inflammatory disease
The ability of malignant tumour cells to escape from primary tumour sites and spread through the circulation to other sites in the body (metastasis) is what makes cancer such a deadly disease. An essential process in metastasis is cell invasion – where tumour cells move into and out of the vasculature. Cell invasion is also a critical event in the migration of white blood cells of the immune system (leukocytes) to sites of inflammation to combat infections. The heparan-sulphate (HS)-degrading enzyme has been shown to play a key role in the degradation of extracellular matrices and its activity strongly correlates with the metastatic capacity of tumour cells and the migratory capacity of leukocytes. We have shown that heparanase is the dominant HS-degrading enzyme in mammalian tissues, making it an attractive drug target.
We are currently working towards:
(1) Further understanding the molecular basis of heparanase function at the structural level.
(2) Defining the dysregulation of heparanase gene expression in cancer and inflammatory disease.
(3) Using heparanase conditional knockout mice in disease models to define the precise role and contribution of heparanase in tumour progression and inflammation (Poon et al., 2014).