The effects of reactive species on the tumorigenic phenotype of human head and neck squamous cell carcinoma (HNSCC) cells.
Sustained inflammation up-regulates the reactive species (RS) generating enzymes inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). While clinical data show that levels of iNOS and COX-2 are increased in epithelium during the transformation of dysplasia to overt head and neck squamous cell carcinoma (HNSCC), the mechanisms by which their overexpression contributes to HNSCC development have not been completely delineated. This study assessed the effects of RS on parameters associated with the HNSCC tumorigenic phenotype inclusive of activation of NF-kappaB (in situ immunostaining and reporter assay) and production of proinflammatory and proangiogenic proteins (ELISA analyses). Our data, which show both reactive oxygen and nitrogen species activated NF-kappaB, and that all RS donors evaluated increased HNSCC cellular production of vascular endothelial growth factor, IL-8 and epidermal growth factor receptor proteins, imply inflammation associated RS promote HNSCC by their abilities to modulate intracellular signaling and affect gene expression.
Bradburn
Jennifer E
JE
Integrated Biomedical Sciences Graduate Program, School of Biomedical Sciences, The Ohio State University College of Medicine, Columbus, OH 43210, USA.
Pei
Ping
P
Kresty
Laura A
LA
Lang
James C
JC
Yates
Allan J
AJ
McCormick
Adam P
AP
Mallery
Susan R
SR
D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D066246:ErbB Receptors / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010084:Oxidation-Reduction; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D020672:I-kappa B Proteins; D016209:Interleukin-8; D016328:NF-kappa B; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A; D066246:ErbB Receptors