Abstract
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) microenvironment by hydrolyzing extracellular poly-γ-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-γ-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-γ-glutamated folate was added to the media. In the presence of penta-γ-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.
Original language | English (US) |
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Pages (from-to) | 867-875 |
Number of pages | 9 |
Journal | Prostate |
Volume | 66 |
Issue number | 8 |
DOIs | |
State | Published - Jun 1 2006 |
Externally published | Yes |
Keywords
- 2-(phosphonomethyl)- pentanedioic acid
- DU-145 cells
- Folate hydrolase activity
- LNCaP cells
ASJC Scopus subject areas
- Oncology
- Urology