2008 Annual Meeting Abstracts

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Il18 Binding Protein Is Produced By Prostate Cancer Cells And Its Levels In Urine And Serum Correlate With Tumor Status.
Kazutoshi Fujita*, Charles M Ewing, Alan W Partin, William B Isaacs, Christian P Pavlovich
Johns Hopkins University, Baltimore, MD

Introduction: Cytokines may play a role in the initiation and progression of prostate cancer. We applied a cytokine antibody array to prostatic fluids, and found interleukin 18 binding protein (IL18Bp), which is secreted in mononuclear cells and is a potent inhibitor of interleukin 18, to be significantly upregulated in cases with large volume disease. We sought to further characterize the association of IL18Bp with prostate cancer and determine its presence in patient serum and urine samples.
Methods:Prostatic fluids from 40 fresh radical prostatectomy specimens were analyzed by human cytokine antibody array. IL18Bp expression was also examined in cell lines, and assessed by ELISA in post-DRE urine and serum samples. IL18Bp expression in the prostate tissues was immunohistochemically examined.
Results:IL18Bp was significantly elevated in prostatic fluid from patients with large vs. small volume prostate cancer in their radical prostatectomy specimens by ELISA (p=0.0158). IL18Bp was expressed and secreted from DU 145 and PC-3, but not from LNCaP and CWR-22, by interferon-γ stimulation cooperatively with TNF-α, interferon-α and interferon β. Immunohistochemical staining showed the positive staining of IL18Bp in prostate cancer cells in the radical prostatectomy specimens. Significant differences in post-DRE urinary IL18Bp levels (normalized by total protein) were found between cases with and without cancer on biopsy (p=0.0181). IL18Bp levels in serum correlated with Gleason score (p=0.0289).
Conclusions:Our finding of elevated IL18Bp secretion from prostate cancer cells suggests an attempt by cancer to escape immune surveillance. IL18Bp may be interesting to study further as a marker of aggressive prostate cancer.

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