[ Title ]
- TNF alpha antagonization alters NOS2 dependent nasopharyngeal carcinoma
tumor growth
[ Author ]
- Muraro, E
Comaro, E
Talamini, R
Turchet, E
Miolo, G
Scalone, S
Militello, L
Lombardi, D
Spazzapan, S
Perin, T
Massarut, S
Crivellari, D
Dolcetti, R
Martorelli, D
[ Abstract ]
- Tumor necrosis factor (TNF alpha) 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, TNF alpha
synthesis associates with poor survival. To explore the effect of the
cytokine on NO production and NOS2 dependent NPC growth, NO2- (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 NO2-. Interestingly, tumor explants
derived NO2- levels were more important in elderly patients in
comparison with juveniles. Endogenous TNF alpha neutralization with an
anti-TNF alpha monoclonal antibody (mAb) successfully inhibited NO2-
synthesis by blood mononuclear cells and tumor explants. Recombinant TNF
alpha (rTNF alpha) enhanced NO2- synthesis and C666-1 NPC cell
proliferation. NOS2 selective inhibition (1400W) and TNF alpha
antagonization with an anti-TNFa mAb potently inhibited rTNF alpha
induced C666-1 proliferation and NOT production. Importantly, primary
tumors treated with the anti-TNF alpha mAb also displayed reduced
proliferation index (Ki67). Altogether, our results define
monocytes/macrophages and the primary tumor as major sources of
circulating NO2- in NPC patients and support the idea that antibody
dependent inhibition of the TNF alpha/NOS2 pathway may alter NPC tumor
growth.
[ URL ]
- http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=Alerting&SrcApp=Alerting&DestApp=WOS&DestLinkType=FullRecord;UT=WOS:000356551600022