Prostate stem cell antigen: A cell surface marker overexpressed in prostate cancer

Departments of ^*Urology, ^‡Howard Hughes Medical Institute, and ^‖Microbiology and Molecular Genetics and Molecular Biology Institute, University of California, Los Angeles, CA 90095; ^¶Section of Hematology-Oncology, Department of Medicine, University of Chicago, Chicago, IL 60637; and ^§Department of Pathology, Beth Israel-Deaconess Medical Center-Harvard Medical School, Boston, MA 02215

Contributed by Owen N. Witte

Abstract

The identification of cell surface antigens is critical to the development of new diagnostic and therapeutic modalities for the management of prostate cancer. Prostate stem cell antigen (PSCA) is a prostate-specific gene with 30% homology to stem cell antigen 2, a member of the Thy-1/Ly-6 family of glycosylphosphatidylinositol (GPI)-anchored cell surface antigens. PSCA encodes a 123-aa protein with an amino-terminal signal sequence, a carboxyl-terminal GPI-anchoring sequence, and multiple N-glycosylation sites. PSCA mRNA expression is prostate-specific in normal male tissues and is highly up-regulated in both androgen-dependent and -independent prostate cancer xenografts. In situ mRNA analysis localizes PSCA expression in normal prostate to the basal cell epithelium, the putative stem cell compartment of the prostate. There is moderate to strong PSCA expression in 111 of 126 (88%) prostate cancer specimens examined by in situ analysis, including high-grade prostatic intraepithelial neoplasia and androgen-dependent and androgen-independent tumors. Flow cytometric analysis demonstrates that PSCA is expressed predominantly on the cell surface and is anchored by a GPI linkage. Fluorescent in situ hybridization analysis localizes the PSCA gene to chromosome 8q24.2, a region of allelic gain in more than 80% of prostate cancers. A mouse homologue with 70% amino acid identity and similar genomic organization to human PSCA has also been identified. These results support PSCA as a target for prostate cancer diagnosis and therapy.

Footnotes

↵ † To whom reprint requests should be addressed at: University of California, School of Medicine, Department of Urology, 66–134 Center for the Health Sciences, 10833 Le Conte Avenue, Los Angeles, CA 90095-1738. e-mail: rreiter{at}urology.medsch.ucla.edu.
Data deposition: The sequence reported in this paper has been deposited in the GenBank database (accession no. AF043498).
ABBREVIATIONS:

PSA,

prostate-specific antigen;

PSMA,

prostate-specific membrane antigen;

RDA,

representational difference analysis;

RT-PCR,

reverse transcriptase-coupled PCR;

SCA-2,

stem cell antigen 2;

PLC,

phospholipase C;

PSCA,

prostate stem cell antigen;

GPI,

glycosylphosphatidylinositol