Novel Proteoglycan-Based Therapies for Breast Cancer
Annual rept. 1 Sep 2000-31 Aug 2001
ARKANSAS UNIV FOR MEDICAL SCIENCES LITTLE ROCK
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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.
- Medicine and Medical Research