Novel Proteoglycan-Based Therapies for Breast Cancer
Abstract
Heparan sulfate proteoglycans (HSPGs) are a new class of tumor suppressors. The focus of this project is 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 acivities of naturally occurring proteoglycans is evaluated. Surprisingly, 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 have been constructed and subcloned cell lines stably expressing the transgenes have been established and are being evaluated. This project is the first attempt to use HSPG genes therapeutically for anti-cancer therapy. Also as a result of this project, a new class of anti-cancer therapeutics called neoglycans have and continue to be developed.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2001
- Accession Number
- ADB281670
Entities
People
- Ralph D. Sanderson
Organizations
- University of Arkansas for Medical Sciences