IL-6/NOS2 inflammatory signals regulate MMP-9 and MMP-2 activity and disease outcome in nasopharyngeal carcinoma patients

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 cri...

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Veröffentlicht in:Tumor biology Jg. 37; H. 3; S. 3505 - 3514
Hauptverfasser: Zergoun, Ahmed-Amine, Zebboudj, Abderezak, Sellam, Sarah Leila, Kariche, Nora, Djennaoui, Djamel, Ouraghi, Samir, Kerboua, Esma, Amir-Tidadini, Zine-Charaf, Chilla, Dalia, Asselah, Fatima, Touil-Boukoffa, Chafia, Merghoub, Taha, Bourouba, Mehdi
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Dordrecht Springer Netherlands 01.03.2016
Springer Nature B.V
Schlagworte:
Adult
Biomedical and Life Sciences
Biomedicine
Cancer Research
Carcinoma
Head & neck cancer
Humans
Inflammation
Interleukin-6 - physiology
Matrix Metalloproteinase 2 - metabolism
Matrix Metalloproteinase 9 - metabolism
Middle Aged
Nasopharyngeal Carcinoma
Nasopharyngeal Neoplasms - enzymology
Nasopharyngeal Neoplasms - mortality
Nasopharyngeal Neoplasms - pathology
Neoplasm Metastasis
NF-kappa B - physiology
Nitric oxide
Nitric Oxide - physiology
Nitric Oxide Synthase Type II - physiology
Nitrites - metabolism
Original Article
Studies
Nasopharyngeal carcinoma
MMP
Inflammation
Nitric oxide
IL-6
ISSN:1010-4283, 1423-0380, 1423-0380
Online-Zugang:Volltext
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Zusammenfassung: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 metalloprotease (MMP) activation and their possible correlation with (NO) · production. We observed a significant increase in IL-6 and nitrite (NO 2 − ) 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, nitrite 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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ISSN:1010-4283
1423-0380
1423-0380
DOI:10.1007/s13277-015-4186-4