Fusobacterium nucleatum の慢性感染による口腔癌細胞の上皮間葉転換

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Objectives: Although several studies have reported the effects of Fusobacterium nucleatum infection in oral cancer cells, the cell infection period ranges from three days to a maximum of eight days. Therefore, the in vitro studies conducted to date may not be enough to mimic the environment of oral cancer, which involves constant exposure to oral commensal bacteria. This study aimed to elucidate the effects of chronic Fusobacterium nucleatum infection on oral cancer cells. Methods: Human tongue squamous cell carcinoma cells were infected with Fusobacterium nucleatum for a 4-week period, and cells at 4-week, 2-week, and no infection were used in the experiments. Results: Chronic Fusobacterium nucleatum infection increased the proliferative, invasive, and migratory capacities, decreased the expression of epithelial markers, and increased the expression of mesenchymal markers in cells in a time-dependent manner. In addition, the cells adapted to a slender and elongated morphology, and cell-to-cell separation was induced, suggesting that epithelial-mesenchymal transition occurs in a time-dependent manner. Furthermore, the mRNA level of CD44, a cancer stem cell marker, was upregulated in a time-dependent manner. However, when the cells were infected with usobacterium nucleatum for four weeks in the presence of dexamethasone, the epithelial-mesenchymal transition induced by Fusobacterium nucleatum infection was inhibited. Conclusions: Epithelial-mesenchymal transition in human tongue squamous cell carcinoma cells was induced in a time-dependent manner by chronic Fusobacterium nucleatum infection and was inhibited by dexamethasone. Routine decontamination of the oral cavity may be crucial for controlling tumor invasion and metastasis.

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