Abstract
Cervical lymph node metastasis causes a poor prognosis in cases of stage T1-T2 squamous cell carcinoma (SCC) of the tongue. Recent studies have reported that cluster of differentiation (CD)147, also known as extracellular matrix metalloproteinase inducer, contributes to tumor progression. The present study evaluated the role of CD147 in the tumorigenesis of SCC of the tongue in vitro, as well as the association between CD147 expression and cervical lymph node metastasis in clinical samples of SCC of the tongue. Tongue SCC cell lines were used to evaluate in vitro tumorigenesis. In addition, 41 patients with clinical stage T1-T2 tongue SCC were assessed with a histopathological analysis. Univariate and multivariate analysis were performed to investigate the risk of cervical lymph node metastasis associated with histopathological findings. In the in vitro study, cell invasiveness was upregulated by S100 calcium-binding protein A9 (S100A9) stimulation and downregulated following CD147-blocking antibody treatment. The univariate and multivariate analyses identified CD147 expression in the invasive tumor front as an independent risk factor for metastasis. It was concluded that CD147 induces tongue carcinoma cell invasion through its interaction with S100A9. Thus, an evaluation of the extent of CD147 expression in cancer cell nests at the invasive tumor front may help in predicting cervical lymph node metastasis in patients with clinical N0 T1-T2 tongue SCC.