Suppression of prostate tumor cell growth by stromal cell prostaglandin D synthase-derived products

Cancer Res. 2005 Jul 15;65(14):6189-98. doi: 10.1158/0008-5472.CAN-04-4439.


Stromal-epithelial interactions and the bioactive molecules produced by these interactions maintain tissue homeostasis and influence carcinogenesis. Bioactive prostaglandins produced by prostaglandin synthases and secreted by the prostate into seminal plasma are thought to support reproduction, but their endogenous effects on cancer formation remain unresolved. No studies to date have examined prostaglandin enzyme production or prostaglandin metabolism in normal prostate stromal cells. Our results show that lipocalin-type prostaglandin D synthase (L-PGDS) and prostaglandin D2 (PGD2) metabolites produced by normal prostate stromal cells inhibited tumor cell growth through a peroxisome proliferator-activated receptor gamma (PPARgamma)-dependent mechanism. Enzymatic products of stromal cell L-PGDS included high levels of PGD2 and 15-deoxy-delta(12,14)-PGD2 but low levels of 15-deoxy-delta(12,14)-prostaglandin J2. These PGD2 metabolites activated the PPARgamma ligand-binding domain and the peroxisome proliferator response element reporter systems. Thus, growth suppression of PPARgamma-expressing tumor cells by PGD2 metabolites in the prostate microenvironment is likely to be an endogenous mechanism involved in tumor suppression that potentially contributes to the indolence and long latency period of this disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Arachidonic Acid / metabolism
  • Cell Growth Processes / physiology
  • Cell Line, Tumor
  • GTP-Binding Proteins / metabolism
  • Humans
  • Intramolecular Oxidoreductases / biosynthesis
  • Intramolecular Oxidoreductases / metabolism*
  • Lipocalins
  • Male
  • PPAR gamma / antagonists & inhibitors
  • PPAR gamma / biosynthesis
  • PPAR gamma / genetics
  • Prostaglandin D2 / metabolism
  • Prostatic Neoplasms / enzymology
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology*
  • Receptors, Immunologic / deficiency
  • Receptors, Immunologic / metabolism
  • Receptors, Prostaglandin / deficiency
  • Receptors, Prostaglandin / metabolism
  • Stromal Cells / enzymology
  • Stromal Cells / metabolism
  • Stromal Cells / pathology
  • Transcriptional Activation


  • Lipocalins
  • PPAR gamma
  • Receptors, Immunologic
  • Receptors, Prostaglandin
  • prostanoid D receptor 1, human
  • Arachidonic Acid
  • GTP-Binding Proteins
  • Intramolecular Oxidoreductases
  • prostaglandin R2 D-isomerase
  • Prostaglandin D2
  • prostaglandin D2 receptor