Review Article Prostate-Specific Membrane Antigen William R. Fair,* Ron S. Israeli, and Warren D.W. Heston Urology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York BACKGROUND. In an effort to discover new prostate-specific antigens (PSAs) to enhance our understanding of the functions and behavior of the prostate and the complex processes involved in prostate tumor progression, the structure and function of the PSM antigen has been elucidated. METHODS. The PSM antigen was recognized using the 7E11–C5.3 monoclonal antibody, generated against the LNCaP human prostate adenocarcinoma cell line. The PSM cDNA was isolated by PCR, using tryptic peptides of immunoprecipitated PSM to design degenerate primers. RESULTS. The prostate specific membrane antigen (PSM) is a 100KD glycoprotein which appears to be a type II integral membrane protein. The protein and cDNA have been exten- sively characterized and the findings reviewed in the report. CONCLUSIONS. PSM, a new prostate antigen is valuable as a marker for hematogenous micro-metastatic tumor dissemination as detected in RT-PCR assays of peripheral blood. PSM has many properties that may be potentially useful as a molecular target in monoclonal antibody directed strategies of tumor imaging and therapy. Prostate 32:140–148, 1997. © 1997 Wiley-Liss, Inc. KEY WORDS: prostate-specific membrane antigen; RT-PCR; PSA INTRODUCTION Adenocarcinoma of the prostate is the most preva- lent noncutaneous malignancy in American men. In 1996, more than 317,000 new cases are expected to be diagnosed, with more than 41,000 attributable deaths [1]. Five-year cause-specific survival rates for patients with localized prostate cancer approximate 88%, while only 29% of patients with metastatic disease survive for 5 years [2]. In patients with clinically lo- calized prostate cancer who undergo definitive treat- ment by either radical prostatectomy or external beam radiotherapy, and who demonstrate patholog- ically organ confined disease (with or without capsu- lar penetration), 12% will subsequently fail biochemi- cally, as evidenced by an elevated serum prostate- specific antigen (PSA) level [3,4]. If diagnosed at an early stage, the survival of patients following radical prostatectomy is excellent [5]; efforts have therefore focused on aggressive screening and on early detec- tion of localized cancers. The increased public and professional awareness and use of serum markers such as PAP and predominantly PSA in part accounts for the rapid increase in the number of cases diag- nosed over the past 8 years. LNCaP CELLS AND THE 7E11–C5.3 ANTIBODY Tissue-specific proteins enable us to study func- tions and properties unique to that particular organ. Horoszewicz et al. [6] previously described a pros- tate-specific IgG1 monoclonal antibody that they termed 7E11–C5.3. This antibody was generated by using cell membranes from the LNCaP prostate can- cer cell line [7] to immunize mice and form hybrido- mas. LNCaP cells were established using a metastatic Abbreviations: PSM, prostate-specific membrane antigen; RT-PCR, reverse transcriptase-polymerase chain reaction; cDNA, comple- mentary DNA: LNCaP, lymph node carcinoma of the prostate; PAP, prostatic acid phosphatase; PSA, prostate specific antigen, kD, kilodalton; SDS, sodium dodecyl sulfate; BPH, benign pros- tatic hypertrophy; CaP, carcinoma of the prostate; PIN, prostatic intraepithelial neoplasia; bFGF, basic fibrinogen growth factor; TGF-, transforming growth factor-; EGF, epidermal growth fac- tor; CT, computed tomography; MRI, magnetic resonance imag- ing. *Correspondence to: Dr. William R. Fair, Urology Service, Depart- ment of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Room C1061, New York, NY 10021. Received 16 April 1996; Accepted 22 April 1996 The Prostate 32:140–148 (1997) © 1997 Wiley-Liss, Inc.