heparitin-sulfate and Prostatic-Hyperplasia

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.. 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.. 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.. 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.

Topics: Adult; beta-Galactosidase; Chondroitin ABC Lyase; Chondroitin Lyases; Chondroitin Sulfates; Chromatography, Ion Exchange; Dermatan Sulfate; Electrophoresis, Cellulose Acetate; Electrophoresis, Polyacrylamide Gel; Extracellular Matrix; Glycosaminoglycans; Glycoside Hydrolases; Heparitin Sulfate; Humans; Hyaluronic Acid; Hyaluronoglucosaminidase; Male; Polysaccharide-Lyases; Prostatic Hyperplasia

To investigate changes in glycosaminoglycan (GAG) profiles in human prostatic tissue.. Seventeen human prostatic samples were examined; five were normal, six hyperplastic and six were cancerous. Prostatic proteoglycans were extracted with 4 mol/L guanidine-HCl containing protease inhibitors. After digestion of the freeze-dried proteoglycan extract with papain, the prostatic GAGs were purified. Total GAGs were measured by a modified dimethylmethylene blue (DMB) method. High-performance liquid chromatography (HPLC) was used to quantify the extracted GAGs.. Six types of GAGs, i.e. chondroitin 4-sulphate (Ch-4S), chondroitin 6-sulphate (Ch-6S), dermatan sulphate (DS), chondroitin, heparan sulphate and hyaluronic acid, were analysed qualitatively and quantitatively. The total amount of GAGs was increased in hyperplastic and cancerous prostates, with the predominant components being DS and Ch-6S in these specimens. The Ch-S:DS ratio in cancerous prostate was significantly higher than that in normal and BPH tissue (P < 0.05). Moreover, chondroitin was increased in hyperplastic prostatic tissue (P < 0.01).. These results suggest that an increase in chondroitin levels may be associated with hyperplastic change and an increase in the Ch-S:DS ratio may be related to the development of malignancy.

Topics: Adult; Aged; Chondroitin Sulfates; Chromatography, High Pressure Liquid; Dermatan Sulfate; Female; Glycosaminoglycans; Heparitin Sulfate; Humans; Hyaluronic Acid; Male; Middle Aged; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms

The glycosaminoglycans of normal, benign hyperplastic and cancerous prostate were studied. In both prostatic hyperplasia and cancer the chondroitin sulfate:dermatan sulfate ratio was increased. In prostatic cancer this increase correlated with both the differentiation and extent of cancer in the prostate. The percentages heparan sulfate and heparan sulfate sulfation were decreased in prostatic cancer. Hyaluronic acid increased with dedifferentiation of the cancer. Histochemically, sulfated glycosaminoglycans were concentrated in the prostatic stroma at the stromal-epithelial interface. The increased chondroitin sulfate:dermatan sulfate ratio may be a nonspecific response or requirement for epithelial growth.

Topics: Adult; Aged; Chondroitin Sulfates; Dermatan Sulfate; Glycosaminoglycans; Heparitin Sulfate; Histocytochemistry; Humans; Hyaluronic Acid; Male; Middle Aged; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Uronic Acids

A study has been made of the glycosaminoglycans (GAG) of the fetus, normal adult, and benign hyperplastic prostate. In the adult normal prostate dermatan sulphate (DS) is the predominant GAG. The central zone has a slightly higher chondroitin sulphate (Ch AC) content than the peripheral zone. Fetal prostates (22-27 weeks gestation) contain no heparan sulphate (HS). Benign prostatic hyperplasia (BPH) has an increased content of Ch AC. On separation of BPH stroma and epithelium, the epithelial fraction contains only Ch AC and DS. HS and hyaluronic acid (HA) are confined to the prostatic stroma.

Topics: Adult; Aged; Aging; Chondroitin Sulfates; Dermatan Sulfate; Electrophoresis, Cellulose Acetate; Epithelium; Glycosaminoglycans; Heparitin Sulfate; Humans; Hyaluronic Acid; Male; Middle Aged; Prostate; Prostatic Hyperplasia