IL-18 is produced by prostate cancer cells and secreted in response to interferons.

Abstract

Murine models have shown that IL-18 has antiangiogenic and antitumor effects, but little is known about IL-18 production in human tumors. We investigated IL-18 expression in clinically localized prostate cancers by immunohistochemistry and showed that 75% of the prostate cancers studied (27/36 cases) presented with tumor cells producing IL-18. Prostate tumor cell lines PC-3, DU 145 and LNCaP synthesized the immature form of IL-18 (p24). IFN-gamma produced in prostate cancers induced caspase-1 mRNA and IL-18 secretion of tumor cell lines, which was inhibited by the cell-permeable Tyr-Val-Ala-Asp-aldehyde caspase-1 inhibitor (YVAD-CHO). Interestingly, IFN-alpha also induced IL-18 secretion of the poorly differentiated cell line PC-3. PC-3 and DU 145, but not the well-differentiated cell line LNCaP, expressed IL-18R alpha (IL-1Rrp) protein and transcripts for IL-18R beta (AcPL). Exogenous IL-18 increased mitochondrial activity of both cell lines evaluated by the tetrazolium (MTT) assay but did not influence their proliferation. This indicated that prostate tumor cells could secrete IL-18 in response to IFN-gamma in the tumor microenvironment and that IL-18 could act as a autocrine/paracrine factor for the tumor. In the cohort of patients studied, IL-18 expression in prostate cancers (with up to 10% of tumor cells stained) was associated with a favorable outcome and equally predictive as pathologic stage on multivariate analysis (log rank test, p = 0.02). Tumor IL-18 production is a novel physiopathologic feature of prostate cancer and appears to be a favorable event in the course of the disease. Modulation of IL-18 production by interferons could have a beneficial clinical effect, which deserves further investigation.

• Authors: Sophie Lebel-Binay, Nicolas Thiounn, Gonzague De Pinieux, Annick Vieillefond, Bernard Debré, Jean-Yves Bonnefoy, Wolf-Herman Fridman, Franck Pagès
• Journal: International journal of cancer (Int J Cancer) Vol. 106 Issue 6 Pg. 827-35 (Oct 10 2003) ISSN: 0020-7136 [Print] United States
• PMID: 12918059 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2003 Wiley-Liss, Inc.

Chemical References

• Antineoplastic Agents
• Caspase Inhibitors
• DNA Primers
• IL18R1 protein, human
• Interferon-alpha
• Interleukin-18
• Interleukin-18 Receptor alpha Subunit
• RNA, Messenger
• Receptors, Interleukin
• Receptors, Interleukin-18
• Tetrazolium Salts
• Thiazoles
• Interferon-gamma
• Prostate-Specific Antigen
• Caspase 1
• thiazolyl blue

Topics

• Antineoplastic Agents (pharmacology)
• Caspase 1 (genetics, metabolism)
• Caspase Inhibitors
• Cell Division (drug effects)
• Cohort Studies
• DNA Primers (chemistry)
• Flow Cytometry
• Gene Expression Regulation, Neoplastic
• Humans
• Immunoenzyme Techniques
• Interferon-alpha (pharmacology)
• Interferon-gamma (pharmacology)
• Interleukin-18 (biosynthesis)
• Interleukin-18 Receptor alpha Subunit
• Male
• Prostate-Specific Antigen (metabolism)
• Prostatic Neoplasms (metabolism, pathology)
• RNA, Messenger (metabolism)
• Receptors, Interleukin (metabolism)
• Receptors, Interleukin-18
• Reverse Transcriptase Polymerase Chain Reaction
• Tetrazolium Salts
• Thiazoles
• Tumor Cells, Cultured (drug effects)