title: Immunomodulatory IL-18 binding protein is produced by prostate cancer cells and its levels in urine and serum correlate with tumor status.
abstract: Cytokines may play a role in the initiation and progression of prostate cancer. A cytokine antibody array was previously applied to prostatic fluid obtained from patients with prostate cancer, and interleukin 18 binding protein (IL-18BP), a potent inhibitor of interleukin 18, was noted to be significantly upregulated in cases with large volume disease. We sought to further characterize the association of IL-18BP with prostate cancer and determine whether IL-18BP levels in patient serum and urine samples had clinical relevance. IL-18BP was expressed and secreted by the prostate cancer cell lines DU145 and PC3 but not by LNCaP and CWR22, upon interferon-γ (IFN-γ) stimulation. IFN-γ-induced secretion of IL-18BP was enhanced by added TNF-α, IFN-α and IFN-β. The IL-18BP secreted from DU145 and PC3 functionally inhibited IL-18. Immunohistochemical analyses showed positive IL-18BP staining in prostate cancer cells as well as in macrophages in radical prostatectomy specimens. Significant differences in urinary IL-18BP levels (normalized by total protein) collected post-DRE were found between cases with and without cancer on biopsy (p = 0.02) and serum IL-18BP levels correlated with Gleason score (p = 0.03). Our finding of elevated IL-18BP secretion from prostate cancer cells suggests an attempt by cancer to escape immune surveillance. IL-18BP merits further study as a marker of aggressive prostate cancer and as a therapeutic target.
authors.affiliation: Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, MD 21224, USA.
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Fujita
authors.forename: Charles M
authors.initials: CM
authors.lastname: Ewing
authors.forename: William B
authors.initials: WB
authors.lastname: Isaacs
authors.forename: Christian P
authors.initials: CP
authors.lastname: Pavlovich
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood* / Q000652:urine*; D045744:Cell Line, Tumor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood* / Q000652:urine*; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000097:blood / Q000276:immunology* / Q000652:urine
chemical_list: D014408:Biomarkers, Tumor; D036341:Intercellular Signaling Peptides and Proteins; C118370:interleukin-18 binding protein