Background: Benign prostatic hyperplasia (BPH) involves qualitative and quantitative alterations in extracellular matrix (ECM) components affecting stromal-epithelial interactions. Glycosaminoglycans (GAGs) are polysaccharide components of the ECM whose role in the development of BPH is under investigation.
Methods: GAGs were extracted from human prostates of normal and BPH origin and were subsequently fractionated through DEAE-sephacel anion exchange chromatography. The isolated GAG fractions were identified through electrophoresis on cellulose acetate membranes and treatment with GAG-degrading enzymes of known specificity. Their size distribution was determined through gradient polyacrylamide gel electrophoresis.
Results: Isolated prostatic GAGs included hyaluronic acid (HA), heparan sulphate (HS), and a mixture of dermatan sulphate (DS) and chondroitin sulphate (CS). The CS/DS ratio was significantly higher in hyperplastic as compared to normal prostates. A difference was also observed with respect to the apparent molecular mass of the DS-CS mixture, which reflects the CS enrichment in BPH. GAGs isolated from hyperplastic prostates were more diverse in size as compared to the corresponding glycans from normal prostates.
Conclusions: The apparent increase in CS and decrease in DS content in prostates of patients with BPH is in good agreement with the pathological manifestation of increased cell proliferation in hyperplastic prostate tissue, since these glycan molecules have been reported to increase and decrease cell proliferation, respectively. Identification of the responsible enzymes involved in the homeostasis of CS and DS may provide alternative targets for pharmacological intervention.
Copyright 2000 Wiley-Liss, Inc.