The role of nitric oxide (NO)• in the development of the metastatic properties of nasopharyngeal carcinoma (NPC) is not fully understood. Previous studies proposed that interleukin-6 (IL-6) would act as regulator of matrix metalloprotease activation in NPC. Recently, we showed that (NO)• was a critical mediator of tumor growth in patients. The aim of this study was to determine the implication of IL-6 in the progression of NPC pathology via MMPs activation and their possible correlation with (NO)• production. We observed a significant increase in IL-6 and nitrites (NO2−) synthesis in patients (n=17) as well as a strong expression of IL-6 and nitric oxide synthase 2 (NOS2) in the analyzed tumors (n=8). In patients’ plasma, a negative correlation associated IL-6 with circulating nitrites (r=−0.33). A negative correlation associated the H-scores of these signals in the tumors (r=−0.47). In patients’ plasma, nitrites synthesis was positively associated with MMP-9 activation (r=0.45), pro-MMP-2 expression (r=0.37) and negatively correlated with MMP-2 activation (r=−0.51). High nitrite levels was associated with better recurrence free survival RFS (p=0.02). Overall our results suggest that the IL-6/NOS2 inflammatory signals are involved in the regulation of MMP-9 and MMP-2 dependent metastatic activity, and that high circulating nitrite levels in NPC patients may constitute a prognostic predictor for survival.
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