Benign hyperplasia of the human prostate is associated with tissue enrichment in chondroitin sulphate of wide size distribution

BACKGROUND. Benign prostatic hyperplasia (BPH) involves qualitative and qua ntitative alterations in extracellular matrix (ECM) components affecting st romal-epithelial interactions. Glycosaminoglycans (GAGs) are polysaccharide components of the ECM whose role in the development of BPH is under invest igation. METHODS. GAGs were extracted from human prostates of normal and BPH origin and were subsequently fractionated through DEAE-sephacel anion exchange chr omatography. The isolated GAG fractions were identified through electrophor esis on cellulose acetate membranes and treatment with GAG-degrading enzyme s of known specificity. Their size distribution was determined through grad ient polyacrylamide gel electrophoresis. RESULTS. Isolated prostatic GAGs included hyaluronic acid (HA), heparan sul phate (HS), and a mixture of dermatan sulphate (DS) and chondroitin sulphat e (CS). The CS/DS ratio was significantly higher in hyperplastic as compare d to normal prostates. A difference was also observed with respect to the a pparent molecular mass of the DS-CS mixture, which reflects the CS enrichme nt in BPH. GAGs isolated from hyperplastic prostates were more diverse in s ize as compared to the corresponding glycans from normal prostates. CONCLUSIONS. The apparent increase in CS and decrease in DS content in pros tates of patients with BPH is in good agreement with the pathological manif estation of increased cell proliferation in hyperplastic prostate tissue, s ince these glycan molecules have been reported to increase and decrease cel l proliferation, respectively. Identification of the responsible enzymes in volved in the homeostasis of CS and DS may provide alternative targets for pharmacological intervention. Prostate 44:104-110, 2000. (C) 2000 Wiley-Lis s, Inc.