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ß-2-Microglobulin Is an Androgen-Regulated Secreted Protein Elevated in Serum of Patients with Advanced Prostate Cancer

Authors' Affiliation: Louis Warschaw Prostate Cancer Center, Cedars-Sinai Medical Center, Los Angeles, California

Requests for reprints: Mitchell Gross, Louis Warschaw Prostate Cancer Center, Cedars-Sinai Medical Center, 8631 West Third Street, Suite 1001E, Los Angeles, CA 90048. Phone: 310-423-7600; Fax: 310-423-1998; E-mail: mitchell.gross{at}cshs.org.

Purpose: A better understanding of secreted proteins may lead to the discovery of new biomarkers, which, along with prostate-specific antigen (PSA), may be useful in the diagnosis and treatment of prostate cancer patients.

Experimental Design: Conditioned medium was collected from LNCaP cells following stimulation with methyltrienolone (R1881), 17ß-estradiol (estradiol), or interleukin-6 and analyzed for differential protein expression with surface-enhanced laser desorption/ionization-time of flight mass spectrometry. Quantitative reverse transcription-PCR, immunoblots, and ELISA were used to measure ß-2-microglobulin (B2M) message and protein levels in cells, conditioned medium, and serum.

Results: Surface-enhanced laser desorption/ionization-time of flight revealed that many peaks were induced or repressed following stimulation with R1881 or estradiol. A peak of interest centered at 11.8 kDa was chosen for additional analysis. Immunodepletion identified the peak of interest as B2M. Reverse transcription-PCR and immunoblots confirmed that PSA and B2M were induced by R1881. However, unlike PSA, B2M was not increased on stimulation with estradiol or interleukin-6. Human B2M is identified in the serum of mice bearing human prostate cancer xenograft. B2M is expressed in human prostate cancer cell lines and tissues. Serum B2M levels are elevated in patients with metastatic, androgen-independent prostate cancer.

Conclusions: B2M is a secreted protein expressed in prostate cancer, which is more specific for androgen stimulation than PSA under the conditions tested. Additional studies are warranted to explore if B2M is as useful marker for prostate cancer. Identification of proteins secreted from cancer cells in preclinical models may be a useful strategy for biomarker discovery.