RAGE Expression and Invasiveness of Oral Squamous Cell Carcinoma Cells Via Differential Expression of Matrix Remodeling Enzymes
Abstract
Clarke D, Yeates E, Davis G, Harward K, Robertson P, Licari FW, Winden DR, Reynolds PR and Arroyo JA
Oral squamous cell carcinoma is an aggressive cancer that affects approximately 30,000 people annually. Tobacco use is known to induce diseases characterized by abnormal oral squamous cell carcinoma cells. The receptor for advanced glycation end-products is a surface receptor that is up-regulated by cigarette smoke in diverse tissue types, including oral squamous cell carcinoma cells. Our objective was to determine the receptor for advanced glycation end-products message and protein expression, cell invasiveness, and potential regulatory enzymes implicated in matrix remodeling during cigarette smoke extract exposure.
Gingiva-derived Ca9-22 cells and tongue-derived Cal27 cells were cultured and exposed to 0.05% cigarette smoke extractfor 24 hours. Cell invasion was determined and cells were lysed for either quantitative polymerase chain reaction or western blot analysis. The receptor for advanced glycation end-products (mRNA and protein) was determined as well as protein expression for metalloprotease 2, metalloprotease 13 and the tissue inhibitor of metalloproteinases.
Treatment of these two cell lines with cigarette smoke extract resulted in: (i) increased receptor for advanced glycation end- products mRNA and protein expression; (ii) increased Ca9-22 and Cal27 cell invasion; (iii) increased metalloprotease 2, metalloprotease 13 and the tissue inhibitor of metalloproteinases in Ca9-22 cells; (iii) decreased metalloprotease 13 and the tissue inhibitor of metalloproteinases in Cal27 cells.
We conclude that cigarette smoke extract increases invasion of oral squamous cell carcinoma cells in a cell dependent fashion. These results can provideinsights into the understanding of oral squamous cell carcinoma cellular behavior in smoke environments.