Upregulation of prostate-specific membrane antigen after androgen-deprivation therapy.
OBJECTIVE
To determine the expression of prostate-specific membrane antigen (PSMA) before and after androgen-deprivation therapy and to compare PSMA expression with prostate-specific antigen (PSA) expression.


METHODS
We studied specimens from 20 patients with prostate cancer undergoing medical or surgical castration or combination androgen-deprivation therapy in whom matched pretreatment and post-treatment tissue specimens were available and 16 patients in whom only a post-treatment specimen was available. The expression of PSMA and PSA in the tissue specimens was determined by immunoperoxidase staining. The extent of staining was calculated by multiplying the percent of antigen-positive tumor cells by the staining intensity to arrive at a stain index for each biomarker. An in vitro study assessed the concentration of PSMA and PSA in extracts of LNCaP cells cultured in the presence or absence of androgen as determined by immunoassays and Western blot analysis.


RESULTS
PSMA reactivity was found to be increased in 55% (11 of 20) of post-treatment primary tissues and 100% (4 of 4) of post-treatment metastatic specimens. In contrast, PSA expression was found to be decreased in 70% (14 of 20) of post-treatment primary and 100% (4 of 4) of post-treatment metastatic specimens. Neither type of androgen-deprivation treatment nor tissue sensitivity to androgen deprivation appeared to influence degree of biomarker expression. PSMA was found to be downregulated and PSA upregulated when LNCaP cells were cultured in the presence of testosterone or dihydrotestosterone.


CONCLUSIONS
The enhanced expression of PSMA in tissues and LNCaP cells after androgen deprivation suggests that PSMA is upregulated in the majority of prostate carcinomas after androgen treatment. The high expression in metastatic tissues strongly suggests that PSMA may be a clinically useful target for antibody-and genetic-directed therapy of prostate cancer that recurs after androgen deprivation. The mechanism whereby androgens suppress the expression of PSMA, and the association of PSMA with the development of hormone-independent prostate cancers, will require further study.
Wright
G L
GL
Department of Microbiology and Immunology, Eastern Virginia Medical School, Norfolk 23501, USA.
Grob
B M
BM
Haley
C
C
Grossman
K
K
Newhall
K
K
Petrylak
D
D
Troyer
J
J
Konchuba
A
A
Schellhammer
P F
PF
Moriarty
R
R
D000726:Androgen Antagonists / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D000954:Antigens, Surface / Q000096:biosynthesis*; D046508:Culture Techniques; D004150:Dipeptidases / Q000096:biosynthesis*; D043425:Glutamate Carboxypeptidase II; D006801:Humans; D008297:Male; D009919:Orchiectomy; D017430:Prostate-Specific Antigen / Q000096:biosynthesis*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000628:therapy*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000502:physiology*
D000726:Androgen Antagonists; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D004150:Dipeptidases; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II; D017430:Prostate-Specific Antigen