No conflicts of interest were declared.
Snail-associated epithelial–mesenchymal transition promotes oesophageal squamous cell carcinoma motility and progression†
Article first published online: 14 APR 2008
Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The Journal of Pathology
Volume 215, Issue 3, pages 330–339, July 2008
How to Cite
Usami, Y., Satake, S., Nakayama, F., Matsumoto, M., Ohnuma, K., Komori, T., Semba, S., Ito, A. and Yokozaki, H. (2008), Snail-associated epithelial–mesenchymal transition promotes oesophageal squamous cell carcinoma motility and progression. J. Pathol., 215: 330–339. doi: 10.1002/path.2365
- Issue published online: 5 JUN 2008
- Article first published online: 14 APR 2008
- Accepted manuscript online: 14 APR 2008 12:00AM EST
- Manuscript Accepted: 2 APR 2008
- Manuscript Revised: 26 MAR 2008
- Manuscript Received: 13 FEB 2008
- Ministry of Health, Labour and Welfare, Japan
- Terry Fox Run Foundation for Cancer Research, Japan
- oesophageal cancer;
- epithelial–mesenchymal transition
The essential contribution of the epithelial–mesenchymal transition (EMT) to carcinoma progression is the loss of their epithelial characters, gain of mesenchymal marker expression, acquisition of migration, invasive activity and capability to pass through the basement membrane. In this study, we aimed to clarify the role of EMT regulator Snail, a zinc finger transcription factor, in human oesophageal squamous cell carcinoma (OESCC). Most OESCC cell lines expressed epithelial cell–cell adhesion molecules such as E-cadherin and claudin-1 and -7; however, TE-8 (Snail-positive) cells expressed mesenchymal marker vimentin but not E-cadherin and claudins. Transduction of ectopic Snail in TE-15 (Snail-negative) cells diminished expression of these epithelial adhesion molecules with promotion of cell migration, invasion and proliferation as well as the shift from cobblestone-like appearance to spindle morphology. In OESCC tissue samples, immunohistochemical analyses revealed that the nuclear Snail expression at the invasive front was correlated with the high levels of vimentin expression (p = 0.0061), which was conversely associated with reduced expressions of E-cadherin (p = 0.023), claudin-1 (p = 0.0246) and claudin-7 (p = 0.0161). Interestingly, elevated Snail expression at the invasive front of the OESCC was associated with higher incidence of lymphatic (p = 0.0143) and venous vessels invasion (p = 0.0029), lymph node metastasis (p = 0.0074) and clinicopathological tumour stage (p = 0.0057). According to the expressions of epithelial and mesenchymal markers, the tumours were subclassified into three groups, the epithelial-type OESCC and the complete or incomplete EMT-type OESCCs. Snail-positive tumours were frequently categorized into the complete- or incomplete-type EMT phenotypes. Our present results suggest the significance of Snail-associated EMT in the progression of OESCC. Snail-induced EMT at the invasive front of the OESCC can be a novel marker for the prediction of metastasis. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.