High expression levels of nuclear factor kappa B and gelatinases in the tumorigenesis of oral squamous cell carcinoma

Abstract

Background. The cellular mechanisms involved in transformation of a premalignant/potentially malignant oral lesion to a malignant one remain unclear. Previous studies have documented a direct involvement of matrix metalloproteinase (MMP) overexpression in the development and progression of head and neck squamous cell carcinoma (HNSCC). MMP activation, particularly MMP2 and MMP9, observed in different cancers, has been shown to be mediated via the transcription factor nuclear factor kappa B (NF-κB). The present study analyzes the clinical significance of gelatinases and NF-κB in various histologic phases of human oral tumor progression. Methods. Methodology included immunohistochemistry for MMP2, MMP9, p50, and p65 components of NF-κB and IκBα (inhibitor κBα). Gelatin zymography was carried out to determine the extent of gelatinolytic activity. Western blotting was used to confirm the gelatinolytic bands of zymogram, and electrophoretic mobility shift assay (EMSA) was carried out to confirm NF-κB activation. Results. A gradual increase was evident in the intensity of the expression and gelatinolytic activity of gelatinase paralleling the histologic progression of malignancy. This finding supports the histologic evidence of tumor invasion occurring in the transition between premalignancy and invasive cancer. Nuclear translocation of NF-κB (p50–p65 form) gradually progresses through the premalignant phase of oral tissue to the invasive phase, showing NF-κB activation during oral tumorigenesis. NF-κB activation correlatively paralleled the pattern of expression of gelatinases. The results of this study suggest a regulatory role for NF-κB on activation of gelatinases during malignant transformation in the oral mucosa.