Wright G L, Grob B M, Haley C, Grossman K, Newhall K, Petrylak D, Troyer J, Konchuba A, Schellhammer P F, Moriarty R
Department of Microbiology and Immunology, Eastern Virginia Medical School, Norfolk 23501, USA.
Urology. 1996 Aug;48(2):326-34. doi: 10.1016/s0090-4295(96)00184-7.
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.
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.
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.
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.
确定雄激素剥夺治疗前后前列腺特异性膜抗原（PSMA）的表达情况，并将PSMA表达与前列腺特异性抗原（PSA）表达进行比较。
我们研究了20例接受药物或手术去势或联合雄激素剥夺治疗的前列腺癌患者的标本，这些患者有治疗前和治疗后的匹配组织标本，另有16例患者仅有治疗后的标本。通过免疫过氧化物酶染色确定组织标本中PSMA和PSA的表达。染色程度通过将抗原阳性肿瘤细胞的百分比乘以染色强度来计算，得出每个生物标志物的染色指数。一项体外研究通过免疫测定和蛋白质印迹分析评估了在有或无雄激素存在的情况下培养的LNCaP细胞提取物中PSMA和PSA的浓度。
发现55%（20例中的11例）治疗后的原发组织和100%（4例中的4例）治疗后的转移标本中PSMA反应性增加。相比之下，发现70%（20例中的14例）治疗后的原发组织和100%（4例中的4例）治疗后的转移标本中PSA表达降低。两种雄激素剥夺治疗类型以及组织对雄激素剥夺的敏感性似乎均未影响生物标志物的表达程度。当LNCaP细胞在睾酮或双氢睾酮存在的情况下培养时，发现PSMA下调而PSA上调。
雄激素剥夺后组织和LNCaP细胞中PSMA表达增强表明，大多数前列腺癌在雄激素治疗后PSMA上调。转移组织中的高表达强烈提示，PSMA可能是雄激素剥夺后复发的前列腺癌抗体和基因导向治疗的一个临床有用靶点。雄激素抑制PSMA表达的机制以及PSMA与激素非依赖性前列腺癌发生的关联，将需要进一步研究。
