Involvement and Regulation of Heparanase in Prostate Cancer Progression
Abstract
Enhanced heparanase expression correlates with metastatic potential, tumor vascularity and reduced postoperative survival of cancer patients. These observations, the anti-cancerous effect of heparanase gene silencing (ribozyme, siRNA) and of heparanase-inhibiting oligosaccharides, peptides and antibodies, as well as the unexpected identification of a single functional heparanase, suggest that the enzyme is a promising target for anti-cancer drug development. Our studies focused on the regulation of heparanase gene expression (i.e., promoter methylation, action of sex steroids, p53) and effect of augmented levels the enzyme on malignant behavior of prostate cancer cells. We designed effective inhibitory strategies, based on recently created chemical and molecular tools (chemically modified heparin species, siRNA-expressing vector), as well as on better understanding of biochemical aspects of heparanase proenzyme activations (inhibitory peptide approach), toward future development of effective anti-cancer therapeutic modalities.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2006
- Accession Number
- ADA448084
Entities
People
- Michael Elkin