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Interleukin (IL)-18, a biomarker of human ovarian carcinoma, is predominantly released as biologically inactive precursor.
MedLine Citation:
PMID:  21061257     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Interleukin (IL)-18 is a pro-inflammatory and immune-enhancing cytokine, which exerts anti-tumor effects in vivo, mediated by the induction of interferon (IFN)γ. We previously reported that IL-18 processing is defective in epithelial ovarian carcinoma (EOC) cells, which secrete an inactive precursor (pro-IL-18) in vitro. In addition, IL-18 was reported as a potential biomarker of EOC. Here, we further investigated its role as a serological marker in human EOC and addressed its possible biological activity in vivo. Our data indicate that immunoreactive IL-18 is increased in EOC patients' sera at diagnosis as compared to age-matched healthy women. IL-18 levels were higher in the ascitic fluids than in sera, suggesting a local production in the peritoneal cavity. Indeed, immunohistochemical analysis of tumors showed IL-18 expression in cytokeratine-postive neoplastic cells, although also scattered histiocytes and some lymphoid cells stained for IL-18. The detection of human IL-18 in sera and ascitic fluids of immunodeficient mice, orthotopically implanted with human EOC cells, further suggested that circulating IL-18 is tumor-derived. However, IL-18 is not an EOC specific biomarker, as increased serum levels were found also in some endometrial cancer patients. By means of a new monoclonal antibody, we characterized IL-18 present in the ascitic fluid as pro-IL-18, which is biologically inactive. Accordingly, IFNγ was not increased in EOC patients' sera and ascitic fluids and showed no correlation with IL-18 levels. Altogether these data indicate that IL-18 in EOC fluids is predominantly tumor-derived, and that its lack of biological activity may represent a mechanism of tumor-escape.
Authors:
Anna Maria Orengo; Marina Fabbi; Loredana Miglietta; Cristian Andreani; Milena Bruzzone; Andrea Puppo; Paolo Cristoforoni; Maria Grazia Centurioni; Marina Gualco; Sandra Salvi; Simona Boccardo; Mauro Truini; Tiziana Piazza; Silvana Canevari; Delia Mezzanzanica; Silvano Ferrini
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2010-11-8
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  -     ISSN:  1097-0215     ISO Abbreviation:  -     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Translational Oncology, Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
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