Aim: To investigate a potential role of S100A4 in esophagus squamous cell carcinoma metastasis (ESCCs).
Methods: Expression of S100A4 and E-cadherin were analyzed in frozen sections from ESCCs (metastasis, n = 28; non-metastasis, n = 20) by reverse transcription-polymerase chain reaction, quantitative polymerase chain reaction and immunohistochemistry. To explore the influence of S100A4 on esophageal cancer invasion and metastasis, S100A4 was overexpressed or silenced by S100A4 siRNA in TE-13 or Eca-109 cells in vitro and in vivo.
Results: We found the mRNA and protein levels of S100A4 expression in ESCCs was significantly upregulated, and more importantly, that expression of S100A4 and E cadherin are strongly negatively correlated in patients who had metastasis. It was indicated that overexpression of S100A4 in TE-13 and Eca-109 cells downregulates the expression of E-cadherin, leading to increased cell migration in vitro, whereas knockdown of S100A4 inhibited cell migration and upregulation of E-cadherin expression. Moreover, the loss of cell metastatic potential was rescued by overexpression of E-cadherin completely. In addition, nude mice inoculated with S100A4 siRNA-transfected cells exhibited a significantly decreased invasion ability in vivo.
Conclusion: S100A4 may be involved in ESCC progression by regulate E-cadherin expression, vector-based RNA interference targeting S100A4 is a potential therapeutic method for human ESCC.
Keywords: E-cadherin; Esophagus squamous cell carcinoma; Gene treatment; Metastasis; S100A4.