Heparan Sulfate Proteoglycans as Therapeutic Agents for Breast Cancer

Heparan sulfate proteoglycans (HSPGs) regulate normal and cancer cell behaviors by binding growth factors, and by mediating cell adhesion and invasion. Current data strongly support the idea that HSPGs are a new class of tumor suppressors. Studies demonstrate the anti-tumor growth properties of three HSPGs, specifically syndecan-1, glypican-1, and betaglycan. Treatment with purified syndecan-1 produces strong growth suppression in multiple myeloma cell lines, a poorly differentiated squamous cell carcinoma cell line, human and murine mammary tumor cell lines, but not normal cell lines. In addition, treatment of multiple myeloma cells with purified syndecan- 1 induces apoptosis. Many tumors display an alteration in cell surface HSPU expression. When syndecan- 1 is lost from the surface of mammary epithelia, the cells lose epithelial morphology, invade collagen gels and show characteristics of neoplastic growth. When transfected with the syndecan- 1 gene, transformed mammary epithelial cells regain morphology and lose neoplastic growth characteristics. In vivo experiments demonstrate reduced tumorigenicity of syndecan- 1 or glypican- 1 expressing multiple myeloma cells and betaglycan expressing breast cancer cells. We propose that HSPGs are excellent candidates for gene therapy applications for the treatment and possible eradication of breast cancer. Therefore, the purpose of the proposed work is to evaluate the affect of HSPG expression on breast cancer growth and progression. This work represents a novel use of HSPGs genes as anti-cancer therapy.