title: IL-6/NOS2 inflammatory signals regulate MMP-9 and MMP-2 activity and disease outcome in nasopharyngeal carcinoma patients.
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.
authors.affiliation: Department of Cell and Molecular Biology, Team Cytokines and Nitric oxide synthases. Faculty of Biology, University Houari Boumediene USTHB, Bab-Ezzouar, Algiers, Algeria.
authors.forename: Ahmed-Amine
authors.initials: AA
authors.lastname: Zergoun
authors.affiliation: Department of Cell and Molecular Biology, Team Cytokines and Nitric oxide synthases. Faculty of Biology, University Houari Boumediene USTHB, Bab-Ezzouar, Algiers, Algeria.
authors.forename: Abderezak
authors.initials: A
authors.lastname: Zebboudj
authors.affiliation: Department of Cell and Molecular Biology, Team Cytokines and Nitric oxide synthases. Faculty of Biology, University Houari Boumediene USTHB, Bab-Ezzouar, Algiers, Algeria.
authors.forename: Sarah Leila
authors.initials: SL
authors.lastname: Sellam
authors.affiliation: Department of Cell and Molecular Biology, Team Cytokines and Nitric oxide synthases. Faculty of Biology, University Houari Boumediene USTHB, Bab-Ezzouar, Algiers, Algeria.
authors.forename: Nora
authors.initials: N
authors.lastname: Kariche
authors.affiliation: Oto-rhyno-laryngology Department, Mustapha Pacha Hospital, Algiers, Algeria.
authors.forename: Djamel
authors.initials: D
authors.lastname: Djennaoui
authors.affiliation: Oto-rhyno-laryngology Department, Mustapha Pacha Hospital, Algiers, Algeria.
authors.forename: Samir
authors.initials: S
authors.lastname: Ouraghi
authors.affiliation: Oncology Department, Centre Pierre et Marie Curie, Algiers, Algeria.
authors.forename: Esma
authors.initials: E
authors.lastname: Kerboua
authors.affiliation: Central Laboratory for Anatomopathology, Mustapha Pacha Hospital, Algiers, Algeria.
authors.forename: Zine-Charaf
authors.initials: ZC
authors.lastname: Amir-Tidadini
authors.affiliation: Central Laboratory for Anatomopathology, Mustapha Pacha Hospital, Algiers, Algeria.
authors.forename: Dalia
authors.initials: D
authors.lastname: Chilla
authors.affiliation: Central Laboratory for Anatomopathology, Mustapha Pacha Hospital, Algiers, Algeria.
authors.forename: Fatima
authors.initials: F
authors.lastname: Asselah
authors.affiliation: Department of Cell and Molecular Biology, Team Cytokines and Nitric oxide synthases. Faculty of Biology, University Houari Boumediene USTHB, Bab-Ezzouar, Algiers, Algeria.
authors.forename: Chafia
authors.initials: C
authors.lastname: Touil-Boukoffa
authors.affiliation: Ludwig Collaborative Laboratory, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065, USA.
authors.forename: Taha
authors.initials: T
authors.lastname: Merghoub
authors.affiliation: Department of Cell and Molecular Biology, Team Cytokines and Nitric oxide synthases. Faculty of Biology, University Houari Boumediene USTHB, Bab-Ezzouar, Algiers, Algeria. mbourouba@usthb.dz.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Bourouba
mesh_terms: D000328:Adult; D002277:Carcinoma; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D016328:NF-kappa B / Q000502:physiology; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000201:enzymology / Q000401:mortality / Q000473:pathology*; D009362:Neoplasm Metastasis; D009569:Nitric Oxide / Q000502:physiology; D052247:Nitric Oxide Synthase Type II / Q000502:physiology*; D009573:Nitrites / Q000378:metabolism
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D016328:NF-kappa B; D009573:Nitrites; D009569:Nitric Oxide; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: IL-6; Inflammation; MMP; Nasopharyngeal carcinoma; Nitric oxide