title: Clinical and experimental approaches to the pathophysiology of interleukin-18 in cancer progression.
abstract: Interleukin-18 (IL-18, interferon [IFN]-gamma-inducing factor) is a proinflammatory cytokine converted to a biologically active molecule by interleukin (IL)-1beta converting enzyme (caspase-1). A wide range of normal and cancer cell types can produce and respond to IL-18 through a specific receptor (IL-18R) belonging to the toll-like receptor family. The activity of IL-18 is regulated by IL-18-binding protein (IL-18bp), a secreted protein possessing the ability to neutralize IL-18 and whose blood level is affected by renal function and is induced by IFNgamma. IL-18 plays a central role in inflammation and immune response, contributing to the pathogenesis and pathophysiology of infectious and inflammatory diseases. Because immune-stimulating effects of IL-18 have antineoplastic properties, IL-18 has been proposed as a novel adjuvant therapy against cancer. However, IL-18 increases in the blood of the majority of cancer patients and has been associated with disease progression and, in some cancer types, with metastatic recurrence risk and poor clinical outcome and survival. Under experimental conditions, cancer cells can also escape immune recognition, increase their adherence to the microvascular wall and even induce production of angiogenic and tumor growth-stimulating factors via IL-18-dependent mechanism. This is particularly visible in melanoma cells. Thus, the role of IL-18 in cancer progression and metastasis remains controversial. This review examines the clinical correlations and biological effects of IL-18 during cancer development and highlights recent experimental insights into prometastatic and proangiogenic effects of IL-18 and the use of IL-18bp against cancer progression.
authors.affiliation: Department of Cell Biology and Histology, Basque Country University School of Medicine and Dentistry, Leioa, Bizkaia 48940, Spain. gcpvivaf@lg.ehu.es
authors.forename: Fernando
authors.initials: F
authors.lastname: Vidal-Vanaclocha
authors.forename: Lorea
authors.initials: L
authors.lastname: Mendoza
authors.forename: Naiara
authors.initials: N
authors.lastname: Telleria
authors.forename: Clarisa
authors.initials: C
authors.lastname: Salado
authors.forename: María
authors.initials: M
authors.lastname: Valcárcel
authors.forename: Natalia
authors.initials: N
authors.lastname: Gallot
authors.forename: Teresa
authors.initials: T
authors.lastname: Carrascal
authors.forename: Eider
authors.initials: E
authors.lastname: Egilegor
authors.forename: Jabier
authors.initials: J
authors.lastname: Beaskoetxea
authors.forename: Charles A
authors.initials: CA
authors.lastname: Dinarello
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D018450:Disease Progression; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology*; D051379:Mice; D009369:Neoplasms / Q000098:blood supply / Q000276:immunology* / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000473:pathology; D019139:Tumor Escape
chemical_list: D020382:Interleukin-18