Heparan Sulfate Proteoglycans as Therapeutic Agents for Breast Cancer

Heparan sulfate proteoglycans (HSPGs) represent a new class of tumor suppressors. The goal of the proposed work is to evaluate the cell growth inhibitory affects and apoptotic potential of HSPG gene therapy in Vitro and in vivo. The first task is to develop breast cancer gene therapy and evaluate in vitro. Syndecan-1 expression was evaluated on several breast cancer cell lines. The results demonstrate that each cell line expresses an abundance and similar levels of syndecan-1. Therefore, DNA encoding a c-myc tag was incorporated into the ectodomain of the syndecan 1 gene. In addition, truncated gene cassettes have been constructed to allow for the secretion of syndecan- I. We will next isolate breast cancer cell lines expressing the engineered gene constructs and determine the effects on tumorigenicity. The second task of the proposal is the in vivo analysis of breast cancer gene therapy. MDA-MB-231 breast tumors were established in SCID mice and treated by electroporation with a plasmid containing the full length syndecan-1 gene.