Involvement and Regulation of Heparanase in Prostate Cancer Progression
Final rept. 19 Jan 2004-18 Jan 2007
HADASSAH MEDICAL ORGANIZATION JERUSALEM (ISRAEL)
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Improvement in prostate cancer patient survival requires the identification of new therapeutic targets, based on a detailed understanding of the biologic mechanisms involved in metastatic dissemination and growth in bone and other target organs. Heparanase HPSE is a predominant mammalian enzyme that cleaves heparan sulfate, the main polysaccharide component of the extracellular matrix ECM. The role of HPSE in sustaining the pathology of malignant tumors is being extensively studied during the last decade. The link between HPSE and prostate carcinoma progression remains less investigated and was disputed in recent publications, favoring or opposing involvement of the enzyme. Here we report that HPSE directly contributes to the prostate tumor take and growth in bone, as well as to its ability to metastasize to distant organs. Inhibitory strategies designed in the course of the research are hoped to develop into effective anti-cancer therapeutic modalities. Knowledge gained on the regulatory machinery of heparanase promoter is of high significance, as a part of general effort to define the exact molecular mechanisms of heparanasedriven prostate tumorigenesis. In summary, our results suggest that in prostate tumorigenesis HPSE may become important molecular marker in clinical decision-making process for prostate tumor patients, as well as a target for intervention.
- Medicine and Medical Research