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- Title
TNF-α Drives Matrix Metalloproteinase-9 in Squamous Oral Carcinogenesis.
- Authors
Hohberger, Laurie; Wuertz, Beverly R. K.; Xie, Hongwei; Griffin, Tim; Ondrey, Frank
- Abstract
Objectives/Hypothesis: It is well known that invasion is a seminal event in the progression of oral and other head and neck carcinoma sites. We have previously demonstrated tumor necrosis factor (TNF)-α and its dependent cytokines are upregulated in saliva during oral carcinogenesis. TNF-dependent events stimulate nuclear factor (NF)-κB and many NF-κB-dependent genes are associated with cancer progression. Materials and Methods: In the present study, we examined NF-κB stimulation of matrix metalloproteinase (MMP)-9 in a precancerous keratinocyte cell line that models leukoplakia (Rhek cells). We stimulated Rhek cells with both TNF-α and phorbol myristate acetate, known stimulants of NF-κB. We then assayed MMP-9 transcription and secretion by luciferase reporter genes, quantitative real-time polymerase chain reaction, and fluorometric enzyme-linked immunosorbent serologic assay. Results: We discovered that the MMP-9 promoter was significantly stimulated by phorbol myristate acetate and TNF-α on luciferase reporter gene assays. Further, we uncovered that functional MMP-9 promoter activation was accompanied by significant increases in MMP-9 gene expression, as judged by quantitative real-time polymerase chain reaction<!-AQ1: Per style, genes are set italic while proteins are roman. Please underline genes.->. Functional activation of the MMP-9 protein was stimulated by TNF-α and PMA on a fluorescent enzyme-linked immunosorbent serologic assay. Finally, we searched our salivary proteomic database for increases in MMP-9 and discovered it was the third most significant protein in salivas of oral cavity cancer patients over normal controls. Conclusions: We conclude the milieu cytokine, TNF-α, has the capacity to provide stimulation of events related to early invasion of oral cavity cancer, as judged by its ability to stimulate MMP-9.
- Publication
Laryngoscope, 2008, Vol 118, Issue 8, p1395
- ISSN
0023-852X
- Publication type
Article
- DOI
10.1097/MLG.0b013e318174e09b