The soluble alpha chain of interleukin-15 receptor: a proinflammatory molecule associated with tumor progression in head and neck cancer.

Abstract

Interleukin (IL)-15 is a proinflammatory cytokine, as it induces the production of inflammatory cytokines [IL-6, tumor necrosis factor alpha (TNFalpha), IL-17, etc.]. A correlation between high intratumoral IL-15 concentrations and poor clinical outcome in lung and head and neck cancer patients has been recently reported. The purpose of this study was to investigate the role of the soluble alpha chain of IL-15 receptor (sIL-15Ralpha), a natural regulator of IL-15, in head and neck cancer. Fifty-three newly diagnosed untreated head and neck cancer patients were included in this study. Quantification of sIL-15Ralpha was performed with a newly developed RIA. Increased serum sIL-15Ralpha concentrations were found in head and neck cancer patients and were closely correlated with poor clinical outcome both in terms of locoregional control and survival even on multivariate analysis. sIL-15Ralpha was mainly produced by tumor cells via proteolytic cleavage of IL-15Ralpha mediated by ADAM-17. A correlation was observed between ADAM-17 expression in tumor cells and serum sIL-15Ralpha concentrations. Surprisingly, sIL-15Ralpha did not act in vitro as an IL-15 antagonist but rather as an enhancer of IL-15-induced proinflammatory cytokines (IL-6, TNFalpha, and IL-17) that may promote tumor progression. This new tumor evasion mechanism based on amplification of the intratumoral inflammatory reaction is probably not restricted to head and neck cancer, as other tumors have been shown to release sIL-15Ralpha. Overall, these results support for the first time an original protumor role of sIL-15Ralpha in cancer.

• Authors: Cécile Badoual, Grégory Bouchaud, Nour El Houda Agueznay, Erwan Mortier, Stéphane Hans, Alain Gey, Fahima Fernani, Séverine Peyrard, Pierre Laurent -Puig, Patrick Bruneval, Xavier Sastre, Ariane Plet, Laure Garrigue-Antar, Françoise Quintin-Colonna, Wolf H Fridman, Daniel Brasnu, Yannick Jacques, Eric Tartour
• Journal: Cancer research (Cancer Res) Vol. 68 Issue 10 Pg. 3907-14 (May 15 2008) ISSN: 1538-7445 [Electronic] United States
• PMID: 18483276 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cross-Linking Reagents
• Interleukin-15
• Interleukin-15 Receptor alpha Subunit
• Protein Isoforms
• ADAM Proteins
• ADAM17 Protein
• ADAM17 protein, human

Topics

• ADAM Proteins (biosynthesis)
• ADAM17 Protein
• Cross-Linking Reagents (pharmacology)
• Disease Progression
• Gene Expression Regulation, Neoplastic
• Head and Neck Neoplasms (pathology)
• Humans
• Inflammation
• Interleukin-15 (metabolism)
• Interleukin-15 Receptor alpha Subunit (blood, chemistry, physiology)
• Models, Biological
• Multivariate Analysis
• Prognosis
• Protein Isoforms
• Radioimmunoassay