Expression of IL-1α correlates with distant metastasis in patients with head and neck squamous cell carcinoma
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Xavier León1,4, Carolina Bothe1, Jacinto García1, Matilde Parreño3, Sonia Alcolea2, Miquel Quer1, Luis Vila2,* and Mercedes Camacho2,*
1 Department of Otorhinolaryngology, Hospital de la Santa Creu i Sant Pau and Universitat Autònoma de Barcelona, Barcelona, Spain
2 Laboratory of Angiology, Vascular Biology and Inflammation, Institute of Biomedical Research (IIB Sant Pau) and Universitat Autònoma de Barcelona, Barcelona, Spain
3 Laboratory of Translational Molecular Oncology, Institute of Biomedical Research (IIB Sant Pau) and Universitat Autònoma de Barcelona, Barcelona, Spain
4 Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Madrid, Spain
* These authors have contributed equally to this work
Mercedes Camacho, email:
Xavier León, email:
Keywords: head and neck cancer, IL-1α, metastasis, prognosis
Received: June 15, 2015 Accepted: September 23, 2015 Published: October 09, 2015
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.
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