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Tumor Biology

, Volume 37, Issue 3, pp 3505–3514 | Cite as

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

  • Ahmed-Amine Zergoun
  • Abderezak Zebboudj
  • Sarah Leila Sellam
  • Nora Kariche
  • Djamel Djennaoui
  • Samir Ouraghi
  • Esma Kerboua
  • Zine-Charaf Amir-Tidadini
  • Dalia Chilla
  • Fatima Asselah
  • Chafia Touil-Boukoffa
  • Taha Merghoub
  • Mehdi Bourouba
Original Article

Abstract

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 (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, 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.

Keywords

IL-6 Nitric oxide MMP Nasopharyngeal carcinoma Inflammation 

Notes

Acknowledgments

This work was supported by the Agence Thématique de Recherche Scientifique en Santé (ATRSS, Algeria) and the MSKCC (Memorial Sloan-Kettering Cancer Center, New York, USA).

Compliance with ethical standards

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Ahmed-Amine Zergoun
    • 1
  • Abderezak Zebboudj
    • 1
  • Sarah Leila Sellam
    • 1
  • Nora Kariche
    • 1
  • Djamel Djennaoui
    • 2
  • Samir Ouraghi
    • 2
  • Esma Kerboua
    • 3
  • Zine-Charaf Amir-Tidadini
    • 4
  • Dalia Chilla
    • 4
  • Fatima Asselah
    • 4
  • Chafia Touil-Boukoffa
    • 1
  • Taha Merghoub
    • 5
  • Mehdi Bourouba
    • 1
  1. 1.Department of Cell and Molecular Biology, Team Cytokines and Nitric oxide synthases. Faculty of BiologyUniversity Houari Boumediene USTHBAlgiersAlgeria
  2. 2.Oto-rhyno-laryngology DepartmentMustapha Pacha HospitalAlgiersAlgeria
  3. 3.Oncology Department, Centre Pierre et Marie CurieAlgiersAlgeria
  4. 4.Central Laboratory for AnatomopathologyMustapha Pacha HospitalAlgiersAlgeria
  5. 5.Ludwig Collaborative LaboratoryMemorial Sloan-Kettering Cancer CenterNew YorkUSA

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