Prostate-specific membrane antigen is a hydrolase with substrate and pharmacologic characteristics of a neuropeptidase.

Carter, Ruth E.; Feldman, Alexis R.; Coyle, Joseph T.

doi:10.1073/pnas.93.2.749

Cited by 336 publications

(208 citation statements)

References 39 publications

Supporting

Mentioning

200

Contrasting

Unclassified

Order By: Relevance

“…36 PSMA has folate hydrolase activity. 1 Therefore, our findings of PSMA expression in endothelial cells associated with neovasculature may indicate that it is functioning to increase folic acid levels at the site of neovasculature formation, so that folic acid can exert its proangiogenic effects (Figure 4). In support of this, PSMA has been reported to coimmunoprecipitate with the caveolae marker, caveolin 1, 37 which also coimmunoprecipitates with eNOS, 38,39 suggesting the in vivo proximity of PSMA and eNOS.…”

Section: Psma Expression In Tumor Neovasculaturementioning

confidence: 84%

See 1 more Smart Citation

Prostate-specific membrane antigen expression in regeneration and repair

et al. 2008

View full text Add to dashboard Cite

Prostate-specific membrane antigen is a type II transmembrane glycoprotein, expressed in benign and neoplastic prostatic tissue as well as endothelial cells of neovasculature from a variety of tumors. The expression of prostate-specific membrane antigen in nonneoplastic neovasculature has not been well studied. Therefore, we studied nonneoplastic reparative and regenerative human tissues, as well as preneoplastic tissue, to determine the presence of prostate-specific membrane antigen-expressing neovasculature. Formalinfixed paraffin-embedded tissue from keloids, granulation tissue from heart valves and pleura, proliferative and secretory endometrium, and Barrett's mucosa with and without dysplasia were stained for the expression of prostate-specific membrane antigen (3E6). Vessels of proliferative, mid-secretory, and late secretory endometrium were consistently strongly positive for prostate-specific membrane antigen expression in all ten cases of each type (100%). Vessels associated with granulation tissue from pleural peels and heart valves were positive in 10 of 12 cases (83%) and 7 of 10 cases (70%), respectively. Keloids had prostate-specific membrane antigen-expressing endothelial cells in 6 of 15 cases (40%). Prostate-specific membrane antigen was not expressed by vessels associated with Barrett's mucosa with low-grade dysplasia (12 foci), high-grade dysplasia (24 foci), or no dysplasia (18 foci). A variety of nonneoplastic neovasculature expresses prostatespecific membrane antigen, including vessels in proliferative endometrium, granulation tissue, and some scars. This is the first study showing that prostate-specific membrane antigen is expressed in neovasculature from physiologic regenerative and reparative conditions. The folate hydrolase activity of prostate-specific membrane antigen may facilitate vasculogenesis and angiogenesis by increasing local availability of folic acid. These findings will enhance our overall understanding of blood vessel development and will enable us to better understand the effects of anti-prostate-specific membrane antigen therapies, which are already being explored in clinical trials.

show abstract

Section: Psma Expression In Tumor Neovasculaturementioning

confidence: 84%

“…Prostate-specific membrane antigen (PSMA) is a 100 kDa type II transmembrane glycoprotein with folate hydrolase 1 and neurocarboxypeptidase activity. 2 Originally, PSMA expression was identified in prostate cancer cells 3 and was subsequently shown to be consistently expressed in prostatic carcinoma as well as benign prostatic tissue.…”

mentioning

confidence: 99%

Prostate-specific membrane antigen expression in regeneration and repair

et al. 2008

View full text Add to dashboard Cite

show abstract

“…NAAG is catabolized to Nacetylaspartate and glutamate by glutamate carboxypeptidase II (GCP II), also known as N-acetyl-alpha-linked acidic dipeptidase (NAALADase; Stauch et al, 1989). GCP II is identical to prostate-specific membrane antigen and intestinal folate hydrolase (Serval et al, 1990;Slusher et al, 1990;Carter et al, 1996;Halsted et al, 1998). GCP II, a cell surface peptidase with its active site in the extracellular space, is expressed primarily by astrocytes in the brain (Berger et al, 1995b;Carter et al, 1996;Schwab, 1996, 1999).…”

Section: Introductionmentioning

confidence: 99%

“…GCP II is identical to prostate-specific membrane antigen and intestinal folate hydrolase (Serval et al, 1990;Slusher et al, 1990;Carter et al, 1996;Halsted et al, 1998). GCP II, a cell surface peptidase with its active site in the extracellular space, is expressed primarily by astrocytes in the brain (Berger et al, 1995b;Carter et al, 1996;Schwab, 1996, 1999). NAAG fulfills most of the criteria for a neurotransmitter or modulator (Kandel et al, 2000); however, its physiological actions are not well understood.…”

Section: Introductionmentioning

confidence: 99%

NAAG Reduces NMDA Receptor Current in CA1 Hippocampal Pyramidal Neurons of Acute Slices and Dissociated Neurons

Bergeron¹,

Coyle

Tsai

et al. 2004

Neuropsychopharmacol

View full text Add to dashboard Cite

N-Acetylaspartylglutamate (NAAG) is an abundant neuropeptide in the nervous system, yet its functions are not well understood. Pyramidal neurons of the CA1 sector of acutely prepared hippocampal slices were recorded using the whole-cell patch-clamp technique. At low concentrations (20 mM), NAAG reduced isolated N-methyl-D-aspartate receptor (NMDAR)-mediated synaptic currents or NMDA-induced currents. The NAAG-induced change in the NMDA concentration/response curve suggested that the antagonism was not competitive. However, the NAAG-induced change in the concentration/response curve for the NMDAR co-agonist, glycine, indicated that glycine can overcome the NAAG antagonism. The antagonism of the NMDAR induced by NAAG was still observed in the presence of LY-341495, a potent and selective mGluR3 antagonist. Moreover, in dissociated pyramidal neurons of the CA1 region, NAAG also reduced the NMDA current and this effect was reversed by glycine. These results suggest that NAAG reduces the NMDA currents in hippocampal CA1 pyramidal neurons.

show abstract

“…1,2 PSMA is an attractive target for immunotherapy because it is highly expressed in normal and neoplastic prostatic tissue and the neovasculature of solid tumors, with limited expression in normal tissue. [3][4][5][6][7] PSMA-specific monoclonal antibodies (MAb) have been used for in vivo diagnostic and therapeutic applications without adverse events.…”

mentioning

confidence: 99%

Induction of autoantibodies to syngeneic prostate‐specific membrane antigen by xenogeneic vaccination

Gregor

Wolchok

Turaga

et al. 2005

Intl Journal of Cancer

View full text Add to dashboard Cite

Prostate-specific membrane antigen (PSMA) is a prototypical differentiation antigen expressed on normal and neoplastic prostate epithelial cells, and on the neovasculature of many solid tumors. Monoclonal antibodies specific for PSMA are in development as therapeutic agents. Methodologies to actively immunize against PSMA may be limited by immunologic ignorance and/or tolerance that restrict the response to self-antigens. Our studies have previously shown that xenogeneic immunization with DNA vaccines encoding melanosomal differentiation antigens induces immunity in a mouse melanoma model. Here we apply this approach to PSMA to establish proof of principle in a mouse model. Immunization with xenogeneic human PSMA protein or DNA induced antibodies to both human and mouse PSMA in mice. Monoclonal antibodies specific for mouse PSMA were generated to analyze antibody isotypes and specificity for native and denatured PSMA at the clonal level. Most antibodies recognized denatured PSMA, but C57BL/6 mice immunized with xenogeneic PSMA DNA followed by a final boost with xenogeneic PSMA protein yielded autoantibodies that reacted with native folded mouse PSMA. Monoclonal antibodies were used to confirm the expression of PSMA protein in normal mouse kidney. These results establish the basis for clinical trials to test PSMA DNA vaccines in patients with solid tumors that either express PSMA directly or that depend on normal endothelial cells expressing PSMA for their continued growth. ' 2005 Wiley-Liss, Inc.

show abstract

Prostate-specific membrane antigen is a hydrolase with substrate and pharmacologic characteristics of a neuropeptidase.

Cited by 336 publications

References 39 publications

Prostate-specific membrane antigen expression in regeneration and repair

Prostate-specific membrane antigen expression in regeneration and repair

NAAG Reduces NMDA Receptor Current in CA1 Hippocampal Pyramidal Neurons of Acute Slices and Dissociated Neurons

Induction of autoantibodies to syngeneic prostate‐specific membrane antigen by xenogeneic vaccination

Contact Info

Product

Resources

About