The Journal of Membrane Biology

, Volume 205, Issue 3, pp 125–128

N-Methyl-D-Aspartate Receptor in Human Prostate Cancer

Article

Abstract

Expression of the N-methyl-D-aspartate receptor (NMDAr) and its involvement in cellular proliferation is well-known in tumors of neuronal tissue, such as glioma and neuroblastoma. We have investigated NMDAr expression in the normal, hyperplastic and neoplastic human prostate by immunohistochemistry. Low stromal NMDAr immunostaining was observed in 2 of 12 (17%) normal prostate specimens, but epithelial NMDAr staining was not seen. Of 18 benign prostatic hyperplasia (BPH) specimens, none had stromal NMDAr staining, but 2 had low and 1 had high epithelial NMDAr immunoreactivity. Moderate to high NMDAr immunostaining was observed in the stroma of 60 of 145 (41%) prostate cancer (PCa) specimens. Epithelial NMDAr staining was low in 26 (18%) and moderate to high in 36 (25%) of 145 PCa specimens. We have also examined the effects of the NMDAr antagonist memantine on the growth of ten human cancer cell lines: four prostate, two breast and four colon. The NMDAr antagonist memantine inhibited in-vitro growth of all ten cell lines, with half-maximal growth-inhibition at 5 to 20 μg/ml (23 to 92 μM) memantine. An NMDA agonist, L-cysteinesulfinic acid, stimulated cellular proliferation of all ten cell lines, with maximal growth-stimulation (30% to 75%, depending on the cell line) observed between doses of 33 to 66 μM. Our data provide evidence for the expression and activity of NMDAr in prostate cancer.

Keywords

NMDA Memantine L-Cysteinesulfinic acid Cancer Prostate Breast Colon 

References

  1. Abdul M., Hoosein N. 2002. Expression and activity of potassium ion channels in human prostate cancer. Cancer Lett. 186:99–106CrossRefPubMedGoogle Scholar
  2. Gonzalez-Cadavid N.F., Ryndin I., Vernet D., Magee T.R., Rajfer J. 2000. Presence of NMDA receptor subunits in the male lower urogenital tract. J. Andrology 21:566–578Google Scholar
  3. Meldrum B.S. 2000. Glutamate as a neurotransmitter in the brain: review of physiology and pathology. J. Nutrition 130:1007S–1015SGoogle Scholar
  4. North W.G., Fay M.J., Du J., Cleary M., Gallagher J.D., McCann F.V. 1997. Presence of functional NMDA receptors in a human neuroblastoma cell line. Mol. Chem. Neuropathol. 30:77–94PubMedCrossRefGoogle Scholar
  5. Parsons C.G., Danysz W., Quack G. 1999. Memantine is a clinically well tolerated N-methyl-D-aspartate (NMDA) receptor antagonist—a review of preclinical data. Neuropharmacology 38:735–767PubMedGoogle Scholar
  6. Rzeski W., Turski L., Ikonomidou C. 2001. Glutamate antagonists limit tumor growth. Proc. Natl. Acad. Sci. USA 98:6372–6377CrossRefPubMedGoogle Scholar
  7. Rzeski W., Ikonomidou C., Turski L. 2002. Glutamate antagonists limit tumor growth. Biochem. Pharmacol. 64:1195–1200CrossRefPubMedGoogle Scholar
  8. Skerry T.M., Genever P.G. 2001. Glutamate signaling in non-neuronal tissues. Trends Pharmacol. Sci. 22:174–181CrossRefPubMedGoogle Scholar
  9. Takhiro T., Lin JH-C., Arcuino G., Gao Q., Yang J., Nedergaard M. 2001. Glutamate release promotes growth of malignant gliomas. Nature Medicine 7:1010–1015Google Scholar
  10. Tariot P.N., Farlow M.R., Grossberg G.T., Graham S.M., McDonald S., Gergel I. 2004. Memantine Study Group. Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA 291:317–324PubMedGoogle Scholar
  11. Yoshioka A., Ikegaki N., Williams M., Pleasure D. 1996. Expression of N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptor genes in neuroblastoma, medulloblastoma, and other cells lines. J. Neurosc. Res. 46:164–178Google Scholar

Copyright information

© Springer Science+Business Media, Inc. 2005

Authors and Affiliations

  1. 1.Edward Via Virginia College of Osteopathic Medicine and Virginia Polytechnic Institute and State UniversityBlacksburgUSA
  2. 2.Biology DepartmentClaflin UniversityOrangeburg

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