Novel Proteoglycan-Based Therapies for Breast Cancer
Abstract
Heparan sulfate proteoglycans (HSPGs) are a new class of tumor suppressors. The focus of this project was to test novel proteoglycan based therapies for the treatment of breast cancer. In the first objective, the ability of neoproteoglycans (nPGs) to mimic the anti-tumor activities of naturally occurring proteoglycans was evaluated. We found that molecules composed of carbodiimide modified GAG chains that differ from nPGs and native proteoglycans in that they are devoid of a protein component inhibit cancer cell viability. These molecules we call neoglycans, inhibit breast cancer cell viability in vitro through the induction of apoptosis. Treatment of established MDA-MB-231 tumors in nude mice with the neoglycan produced from chondroitin sulfate reduced or abolished tumors following a single dose without any apparent toxicity. In the second objective, a gene therapy approach is tested utilizing the HSPG gene syndecan-1. Tagged full length and truncated human syndecan-1 genes were constructed and subcloned cell lines stably expressing the transgenes were established, characterized and evaluated. Overexpression of syndecan-1 had no detectable effect on growth of the MDA cells in culture or in preliminary experiments in mice.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2002
- Accession Number
- ADA410793
Entities
People
- Ralph D. Sanderson
Organizations
- University of Arkansas for Medical Sciences