Prostate specific membrane antigen (PSMA) expression gives prostate cancer cells a growth advantage in a physiologically relevant folate environment in vitro

Prostate. 2006 Jun 1;66(8):867-75. doi: 10.1002/pros.20361.


Background: Prostate specific membrane antigen (PSMA) expression is correlated with stage and grade of prostate cancer suggesting that it confers a growth advantage. We studied if PSMA folate hydrolase activity provides cells a growth advantage in a low folate (LF) micro-environment by hydrolyzing extracellular poly-gamma-glutamated folate to a form that cells can import.

Methods: Proliferation of LNCaP and DU-145 cells was assessed in media containing low (LF), physiological (PF), or high (HF) folate with or without penta-gamma-glutamated folate and a PSMA specific folate hydrolase inhibitor, 2-(phosphonomethyl)-pentanedioic acid (2-PMPA).

Results: LNCaP cells, which express PSMA, and DU-145 cells, which do not, displayed decreased proliferation when grown in LF or PF compared to HF media. This reduction in proliferation was eliminated in LNCaP cells when penta-gamma-glutamated folate was added to the media. In the presence of penta-gamma-glutamated folic acid DU-145 cells displayed increased growth but this was still significantly lower than growth in HF medium. Addition of 2-PMPA attenuated the increased growth seen in LNCaP cells but had no effect on DU-145 cell growth.

Conclusions: The folate hydrolase activity of PSMA may provide a growth advantage in LF and PF environments.

Publication types

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

MeSH terms

  • Antigens, Surface / physiology*
  • Cell Line, Tumor
  • Cell Proliferation* / drug effects
  • Chromatography, High Pressure Liquid
  • Culture Media, Conditioned
  • Glutamate Carboxypeptidase II / antagonists & inhibitors
  • Glutamate Carboxypeptidase II / physiology*
  • Humans
  • Male
  • Organophosphorus Compounds / pharmacology
  • Prostate-Specific Antigen / analysis
  • Prostate-Specific Antigen / genetics
  • Prostate-Specific Antigen / physiology*
  • Prostatic Neoplasms / chemistry
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / physiopathology*
  • Pteroylpolyglutamic Acids / analysis
  • Pteroylpolyglutamic Acids / pharmacology*
  • Pteroylpolyglutamic Acids / physiology*


  • 2-(phosphonomethyl)pentanedioic acid
  • Antigens, Surface
  • Culture Media, Conditioned
  • Organophosphorus Compounds
  • Pteroylpolyglutamic Acids
  • FOLH1 protein, human
  • Glutamate Carboxypeptidase II
  • Prostate-Specific Antigen