TNFα antagonization alters NOS2 dependent nasopharyngeal carcinoma tumor growth

Bourouba, Mehdi; Maffei, Joseph S.; Chila, Dalia; Djennaoui, Djamel; Asselah, F.; Amir-Tidadini, Zine-Charef; Touil-Boukoffa, Chafia; Zaman, Muhammad H.

doi:10.1016/j.cyto.2015.04.003

Cited by 10 publications

(10 citation statements)

References 46 publications

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“…As several types of cells may generate nitrites and secrete IL-6 in the nasopharyngeal TME [5, 13], we assessed the levels of these molecules in supernatant of NPC tumor explants following 24h culture. Griess and ELISA tests showed that the biopsies released high amounts of nitrites and IL-6 in the culture supernatants (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Our previous studies showed that the TNF-α/NOS2 inflammatory pathway supported tumor growth in-vitro and in patients, and that TNF-α was not the sole responsible for NOS2 activation [4, 5]. We speculated then on the significance of the large differences in nitrite production observed among the tested patients and their possible role in the acquisition of metastatic features or tumor elimination.…”

Section: Discussionmentioning

confidence: 99%

“…This expression was concomitant with the activation of the IL-6 and of the NOS2 genes in the TME, an indicator of nitrosative stress and the principal source of nitric oxide in nasopharyngeal tumors. Possibly, the activated tumor associated macrophages (TAM) infiltrating the nasopharyngeal TME would constitute, beside the tumor cells, the major source of both molecules as indicated by the strong signals detected by immunohistochemistry in the tumor and the stroma, and by our recent observations reporting massive CD68 staining in the TME and increased capacity of monocytes/macrophages from cancer patients to synthesize nitrites [5]. …”

Section: Discussionmentioning

confidence: 99%

“…These processes appear to be intricate in a way to ensure their mutual amplification in a cross-talk involving the tumor and cells infiltrating the TME. Indeed several cross-amplifying signals have been described to associate a) NOS2 expression to NF-κB activation and IL-6 synthesis; b) NF-κB activation to EBV LMP1 oncogene expression; c) LMP1 signaling to IL-6 induction and Stat-3 activation; d) IL-6 mediated perpetuation of Stat-3 activity to LMP1 expression and e) IL-6 signaling to NF-κB mediated NOS2 induction [5, 33, 40–42]. …”

Section: Discussionmentioning

confidence: 99%

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

et al. 2015

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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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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

et al. 2015

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“…30,41,42 However, in our study, we found TNF-α, another new molecular positively correlated with COX-2 by RNA-Seq. Bourouba 43 showed that TNF-α promotes tumor growth via a NOS2-dependent mechanism in NPC. 43 This is the first time to demonstrate TNF-α was upregulated in CAF in NPC.…”

Section: Discussionmentioning

confidence: 99%

High COX‐2 expression in cancer‐associated fibiroblasts contributes to poor survival and promotes migration and invasiveness in nasopharyngeal carcinoma

Zhu

Chen

Zeng

et al. 2019

Molecular Carcinogenesis

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Nasopharyngeal carcinoma (NPC) has the highest rate of metastasis among head and neck cancers, and distant metastasis is the major reason for treatment failure. We have previously shown that high cyclooxygenase‐2 (COX‐2) expression is associated with a poor prognosis of patients with NPC and inhibits chemotherapy‐induced senescence in NPC cells. In this study, we found that COX‐2 was upregulated in cancer‐associated fibroblasts (CAFs) derived from NPC by RNA‐Seq. Furthermore, elevated COX‐2 expression in CAF was detected in NPC patients with poor survival and distant metastasis by using immunohistochemistry. Then, we identified that COX‐2 is highly expressed in CAF at the distant metastasis site in seven paired NPC patients. High expression of COX‐2 and secretion of prostaglandin E2, a major product catalyzed by COX‐2 in fibroblasts, promotes migration and invasiveness of NPC cells in vitro. On the contrary, inhibition of COX‐2 has the opposite effect in vitro as well as in the COX‐2−/− mouse with the lung metastasis model in vivo. Mechanistically, we discovered that COX‐2 elevates tumor necrosis factor‐α expression in CAF to promote NPC cell migration and invasiveness. Overall, our results identified a novel target in CAF promoting NPC metastasis. Our findings suggested that high expression of COX‐2 in CAF may serve as a new prognostic indicator for NPC metastasis and provide the possibility of targeting CAF for treating advanced NPC.

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Potential causal links of long‐term exposure to PM_2.5 and its chemical components with the risk of nasopharyngeal carcinoma recurrence: A 10‐year cohort study in South China

Sun,

Lin,

Yao

et al. 2024

Intl Journal of Cancer

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There is a lack of evidence from cohort studies on the causal association of long‐term exposure to ambient fine particulate matter (PM2.5) and its chemical components with the risk of nasopharyngeal carcinoma (NPC) recurrence. Based on a 10‐year prospective cohort of 1184 newly diagnosed NPC patients, we comprehensively evaluated the potential causal links of ambient PM2.5 and its chemical components including black carbon (BC), organic matter (OM), sulfate (SO42−), nitrate (NO3−), and ammonium (NH4+) with the recurrence risk of NPC using a marginal structural Cox model adjusted with inverse probability weighting. We observed 291 NPC patients experiencing recurrence during the 10‐year follow‐up and estimated a 33% increased risk of NPC recurrence (hazard ratio [HR]: 1.33, 95% confidence interval [CI]: 1.02–1.74) following each interquartile range (IQR) increase in PM2.5 exposure. Each IQR increment in BC, NH4+, OM, NO3−, and SO42− was associated with HRs of 1.36 (95%CI: 1.13–1.65), 1.35 (95%CI: 1.07–1.70), 1.33 (95%CI: 1.11–1.59), 1.32 (95%CI: 1.06–1.64), 1.31 (95%CI: 1.08–1.57). The elderly, patients with no family history of cancer, no smoking history, no drinking history, and those with severe conditions may exhibit a greater likelihood of NPC recurrence following exposure to PM2.5 and its chemical components. Additionally, the effect estimates of the five components are greater among patients who were exposed to high concentration than in the full cohort of patients. Our study provides solid evidence for a potential relationship between long‐term exposure to PM2.5 and its components and the risk of NPC recurrence.

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TNFα antagonization alters NOS2 dependent nasopharyngeal carcinoma tumor growth

Cited by 10 publications

References 46 publications

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

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

High COX‐2 expression in cancer‐associated fibiroblasts contributes to poor survival and promotes migration and invasiveness in nasopharyngeal carcinoma

Potential causal links of long‐term exposure to PM_2.5 and its chemical components with the risk of nasopharyngeal carcinoma recurrence: A 10‐year cohort study in South China

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TNFα antagonization alters NOS2 dependent nasopharyngeal carcinoma tumor growth

Cited by 10 publications

References 46 publications

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

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

High COX‐2 expression in cancer‐associated fibiroblasts contributes to poor survival and promotes migration and invasiveness in nasopharyngeal carcinoma

Potential causal links of long‐term exposure to PM2.5 and its chemical components with the risk of nasopharyngeal carcinoma recurrence: A 10‐year cohort study in South China

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Potential causal links of long‐term exposure to PM_2.5 and its chemical components with the risk of nasopharyngeal carcinoma recurrence: A 10‐year cohort study in South China