Epithelial to mesenchymal transition in head and neck squamous carcinoma

BACKGROUND Epithelial–mesenchymal transformations (EMT) are critical for the invasion, progression, and metastasis of epithelial carcinogenesis. The role of EMT in head and neck squamous carcinoma (HNSC) tumorigenesis remains unexplored. In the current study, the expressions of several factors associated with the induction of EMT in HNSC cell lines and tumor specimens were investigated to define their functional and pathologic role in HNSC. METHODS Eleven HNSC cell lines and 50 primary tumor tissue specimens formed the materials of this study. Western blot analysis as well as immunohistochemical, and functional techniques were used to assess the status of activated Src (p-Src), E-cadherin, and vimentin in both cell lines and tumor tissues and the results were correlated with patients' clinicopathologic parameters. RESULTS The results demonstrated the inverse expression of p-Src and E-cadherin in the majority of cell lines and in primary tumor tissues compared with normal squamous mucosa. Elevated levels of p-Src were accompanied by down-regulation of E-cadherin and the expression of vimentin in epithelial tumor cells. In vitro inhibition of Src led to E-cadherin reexpression and increased cell contact in squamous carcinoma cell lines. Immunophenotypic analysis of these markers in primary tumor tissues demonstrated a significant correlation between increased p-Src, decreased E-cadherin, and vimentin expression and aggressive tumor features including penetrating invasive fronts, high-grade sarcomatoid transformation, and lymph node metastasis. CONCLUSIONS The results of the current study indicate that Src and E-cadherin may play an important role in EMT, invasion, and aggressive clinicopathologic features of HNSC. These proteins may be targeted for the therapeutic intervention of patients with HNSC. Cancer 2008. © 2008 American Cancer Society.