Heparan Sulfate Proteoglycans as Therapeutic Agents for Breast Cancer
Abstract
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 HSPG syndecan-l has proven to be a powerful inhibitor of tumor cell growth and loss of expression has been correlated with a poor prognosis in some cancers. Therefore, two c-myc tagged syndecan-l gene cassettes have been constructed for the expression of syndecan-l on the cell surface or for secretion and these constructs have been transfected into MDA-MB-23l cells and subcloned cell lines established. The MDA-MB-23l cells that overexpress syndecan-l on the cell surface or secrete syndecan-l grow at the same rate as cells transfected with empty vector however, in the absence of serum, the cells secreting syndecan-l grow much slower suggesting a less transformed phenotype. However, both the cells that overexpress syndecan-l on the cell surface and the cells that secrete syndecan-l produce more colonies in soft agar than the vector only transfected control cells. Therefore, at the present time, the in vitro data are conflicting however, we have initiated in vivo studies to definitively determine if overexpression or secretion of syndecan-l decreases tumorigenicity. This project is the first to use HSPG genes for anticancer therapy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2001
- Accession Number
- ADB282152
Entities
People
- Carla Pumphrey
- Ralph D. Sanderson
Organizations
- University of Arkansas for Medical Sciences