title: Expression of IL-1α correlates with distant metastasis in patients with head and neck squamous cell carcinoma.
abstract: The presence of IL-1 in human cancers is associated with aggressive tumor biology but its prognostic value is unknown. We studied whether IL-1α expression is a prognostic marker of distant metastasis in patients with head and neck squamous cell carcinoma (HNSCC). IL-1α mRNA and protein levels were determined in tumor samples and cancer cell lines using RT-PCR and ELISA. The effects of constitutive IL-1α expression by tumor lines were characterized. IL-1α mRNA and protein secretion were higher in tumor samples from patients who later developed distant metastasis than in patients who did not. By using distant metastasis as a dependent variable, patients were classified into two categories of IL-1α transcript-levels. The high-IL-1α group had a significantly lower five-year distant metastasis-free survival than the low-IL-1α group [70.0% (CI 95%: 55.9-84.1%) vs 94.7% (CI 95%:90.2-99.2%)]. When IL-1α transcript-levels were combined with clinical factors related to tumor metastasis, the predictive power of the model increased significantly. Additionally, transcript levels of IL-1α correlated significantly with those of the IL-1 family genes and genes related to the metastatic process. IL-1 treatment of microvascular endothelial cells increased adhesion of HNSCC cells but no differences were found based on constitutive IL-1α expression by tumor cells. Nevertheless, IL-1α produced by tumor cells effectively increased their transmigration across the endothelium. We found a significant relationship between IL-1α expression and development of distant metastasis in HNSCC patients. IL-1α expression could help to define a subset of patients at high risk of distant metastasis who could benefit from adjuvant treatment.
authors.affiliation: Department of Otorhinolaryngology, Hospital de la Santa Creu i Sant Pau and Universitat Autònoma de Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Madrid, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: León
authors.affiliation: Department of Otorhinolaryngology, Hospital de la Santa Creu i Sant Pau and Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Bothe
authors.affiliation: Department of Otorhinolaryngology, Hospital de la Santa Creu i Sant Pau and Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Jacinto
authors.initials: J
authors.lastname: García
authors.affiliation: Laboratory of Translational Molecular Oncology, Institute of Biomedical Research (IIB Sant Pau) and Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Matilde
authors.initials: M
authors.lastname: Parreño
authors.affiliation: Laboratory of Angiology, Vascular Biology and Inflammation, Institute of Biomedical Research (IIB Sant Pau) and Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Alcolea
authors.affiliation: Department of Otorhinolaryngology, Hospital de la Santa Creu i Sant Pau and Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Miquel
authors.initials: M
authors.lastname: Quer
authors.affiliation: Laboratory of Angiology, Vascular Biology and Inflammation, Institute of Biomedical Research (IIB Sant Pau) and Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Vila
authors.affiliation: Laboratory of Angiology, Vascular Biology and Inflammation, Institute of Biomedical Research (IIB Sant Pau) and Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Camacho
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000556:secondary / Q000628:therapy; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D018572:Disease-Free Survival; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D006801:Humans; D053582:Interleukin-1alpha / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018570:Risk Assessment; D012307:Risk Factors; D015398:Signal Transduction; D000077195:Squamous Cell Carcinoma of Head and Neck; D013997:Time Factors; D057705:Transendothelial and Transepithelial Migration; D014162:Transfection; D016896:Treatment Outcome
chemical_list: C508584:IL1A protein, human; D053582:Interleukin-1alpha; D012333:RNA, Messenger
keywords: IL-1α; head and neck cancer; metastasis; prognosis