Pentosan polysulfate decreases prostate smooth muscle proliferation and extracellular matrix turnover

S. J. Elliot, B. H. Zorn, D. G. Mcleod, J. W. Moul, L. Nyberg, L. J. Striker, G. E. Striker

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Benign prostatic hyperplasia (BPH) involves proliferation of smooth muscle cells and increased deposition of extracellular matrix (ECM). We recently found that pentosan polysulfate (PPS) has marked effects on growth and ECM of smooth muscle cells derived from vascular tissues. We examined smooth muscle cells cultured from human prostates and the effects of PPS on their growth and ECM production. Fragments of surgical prostatectomy specimens were diced, digested with collagenase (0.01%), and placed in culture medium supplemented with 20% fetal bovine serum. Outgrowths of elongated cells were characterized by light microscopic examination and immunohistochemical techniques by the presence of F-actin, α-smooth muscle actin, and myosin, which is a characteristic of smooth muscle cells. Two independent isolates were propagated, and growth curves and ECM production were assessed in the presence and absence of PPS (10 or 100 μg/ml). PPS decreased cell number beginning at day 1 and throughout the incubation period, up to 4 days. The amount of the ECM degradative enzymes, metalloproteinases MMP-9 and MMP-2, was examined by zymography. PPS did not alter the amount of MMP-2 in the supernatants but MMP-9 was increased 234.4 ± 17.23-fold over control cells. Tissue inhibitor of MMP (TIMPS), examined by reverse zymography, increased 200% over control. The amount of αI type (IV) and αI type (I) collagen released in the supernatant, measured by ELISA, significantly decreased in PPS-treated cultures. In conclusion, we found that the administration of PPS decreased proliferation as well as ECM production in prostate smooth muscle. Since smooth muscle proliferation and ECM are involved in the pathophysiology of BPH, PPS may have therapeutic potential.

Original languageEnglish (US)
Pages (from-to)138-142
Number of pages5
JournalProstate Cancer and Prostatic Diseases
Volume6
Issue number2
DOIs
StatePublished - Jul 15 2003

Keywords

  • Benign prostatic hyperplasia
  • Extracellular matrix
  • Matrix metalloprotemases (MMP)
  • Pentosan polysulfate
  • Tissue inhibitor of MMP

ASJC Scopus subject areas

  • Oncology
  • Urology

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