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.
Highlights
Loco-regional control of head and neck squamous cell carcinoma (HNSCC) has improved in the last decades thanks to more aggressive surgical techniques, improvements in radiotherapy, and the development of new antitumoral drugs
IL-1α transcript levels are associated with the presence of distant metastasis
We examined the expression of IL1α in tumoral samples from HNSCC patients with and without distant metastasis by quantitative RT-PCR (Figure 1A)
Summary
Loco-regional control of head and neck squamous cell carcinoma (HNSCC) has improved in the last decades thanks to more aggressive surgical techniques, improvements in radiotherapy, and the development of new antitumoral drugs. Tumor www.impactjournals.com/oncotarget metastasis is a sequential multi-step process requiring detachment of individual tumor cells from the adjacent tumor and stromal cells, the invasion and progression through the extracellular matrix, the intravasation into lymphatic or vascular vessels, survival in regional or systemic circulation, and implantation and proliferation into regional neck nodes or distant tissues [2, 3]. All these steps are tightly regulated by cell-associated and soluble mediators. One of these effects is the promotion of metastasis, an effect which has been related with several molecules expression, such as desmoplakin [4], E-cadherin and vimentin [5, 6], αB-crystallin (HspB5) [7] or IL-α [8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
