Accession Number:

ADB264002

Title:

Novel Proteoglycan-Based Therapies for Breast Cancer

Descriptive Note:

Annual rept. 1 Sep 1999-31 Aug 2000

Corporate Author:

ARKANSAS UNIV FOR MEDICAL SCIENCES LITTLE ROCK

Personal Author(s):

Report Date:

2000-09-01

Pagination or Media Count:

14.0

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 activities of naturally occurring proteoglycans is evaluated. In the first year we have successfully produced nPGs with different glycosaminoglycan chains coupled to a protein scaffold. SDS-PAGE analysis confirms nPG production and indicates contamination with glycosaminoglycan chains not coupled to protein. nPG is isolated by size exclusion chromatography and the resulting fractions evaluated for anti-cancer activity. Surprisingly, the low molecular weight fractions, containing glycosaminoglycan chains only, reduce breast cancer cell viability while the nPG containing fractions do not. Therefore, neoglycans, possibly composed of glycosaminoglycan chains coupled to each other, were produced and these reduce breast cancer cell viability. 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 initial studies in mice completed, with inconclusive results. This project is the first attempt to use HSPG genes therapeutically and to produce nPGs and neoglycans for anti-cancer therapy. Results of this first year of work highlight the potential of this strategy.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE