TNFα antagonization alters NOS2 dependent nasopharyngeal carcinoma tumor growth
| Autor: | Zine-Charef Amir-Tidadini, Dalia Chila, Muhammad H. Zaman, Ahmed-Amine Zergoun, Fatima Asselah, Chafia Touil-Boukoffa, Djamel Djennaoui, Mehdi Bourouba, Joseph S. Maffei |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Adult
medicine.medical_specialty Aging Proliferation index Adolescent medicine.medical_treatment Immunology Nitric Oxide Synthase Type II Inflammation Biology Nitric Oxide Biochemistry Peripheral blood mononuclear cell Young Adult Internal medicine medicine Immunology and Allergy Humans Molecular Biology Cells Cultured Cell Proliferation Nasopharyngeal Carcinoma Cell growth Tumor Necrosis Factor-alpha Macrophages Carcinoma Antibodies Monoclonal Nasopharyngeal Neoplasms Hematology Middle Aged medicine.disease Primary tumor Cytokine Endocrinology Ki-67 Antigen Nasopharyngeal carcinoma Cancer research Leukocytes Mononuclear Tumor necrosis factor alpha Female medicine.symptom |
| Zdroj: | Cytokine. 74(1) |
| ISSN: | 1096-0023 |
| Popis: | Tumor necrosis factor (TNFα) is a pro-inflammatory cytokine which mediates via nitric oxide (NO) several carcinogenic processes. Increasing evidences suggest that NO promotes inflammation induced growth of nasopharyngeal carcinoma (NPC). In patients, TNFα synthesis associates with poor survival. To explore the effect of the cytokine on NO production and NOS2 dependent NPC growth, NO 2 − (nitrite) producing cells in patients were analyzed in vitro . We observed that patients’ monocytes/macrophages (Mo/Ma) and primary tumor biopsies synthesized significant amounts of NO 2 − . Interestingly, tumor explants derived NO 2 − levels were more important in elderly patients in comparison with juveniles. Endogenous TNFα neutralization with an anti-TNFα monoclonal antibody (mAb) successfully inhibited NO 2 − synthesis by blood mononuclear cells and tumor explants. Recombinant TNFα (rTNFα) enhanced NO 2 − synthesis and C666-1 NPC cell proliferation. NOS2 selective inhibition (1400W) and TNFα antagonization with an anti-TNFα mAb potently inhibited rTNFα induced C666-1 proliferation and NO 2 − production. Importantly, primary tumors treated with the anti-TNFα mAb also displayed reduced proliferation index (Ki67). Altogether, our results define monocytes/macrophages and the primary tumor as major sources of circulating NO 2 − in NPC patients and support the idea that antibody dependent inhibition of the TNFα/NOS2 pathway may alter NPC tumor growth. |
| Databáze: | OpenAIRE |
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