Incomplete epithelial-mesenchymal transition in p16-positive squamous cell carcinoma cells correlates with β-catenin expression

• Published in: Anticancer research 2014-12, Vol.34 (12), p.7061-7069
• Main Authors: Umbreit, Claudia, Flanjak, Julia, Weiss, Christel, Erben, Philipp, Aderhold, Christoph, Faber, Anne, Stern-Straeter, Jens, Hoermann, Karl, Schultz, Johannes David
• Format: Article
• Language: English
• Subjects: beta Catenin - biosynthesis; Biomarkers, Tumor - biosynthesis; Cadherins - biosynthesis; Carcinoma, Squamous Cell - pathology; Cell Adhesion - genetics; Cell Line, Tumor; Cyclin-Dependent Kinase Inhibitor p16; Enzyme-Linked Immunosorbent Assay; Epidermal Growth Factor - pharmacology; Epithelial-Mesenchymal Transition - genetics; Gene Expression Regulation, Neoplastic; Head and Neck Neoplasms - pathology; Humans; Immunohistochemistry; Neoplasm Proteins - biosynthesis; Neoplasm Proteins - genetics; Squamous Cell Carcinoma of Head and Neck; Transforming Growth Factor beta1 - pharmacology; Vimentin - biosynthesis
• ISSN: 1791-7530

The epithelial-mesenchymal transition (EMT) is suggested to be a crucial factor for the development of an invasive and metastatic cell phenotype, which is characterized by down-regulation of epithelial adhesive proteins (e.g. E-cadherin) and induction of mesenchymal proteins (e.g. vimentin). Therefore, there is a great clinical interest to specify this phenotype. Different growth factors induce EMT, such as epithelial growth factor (EGF) and transforming growth factor beta 1 (TGFβ1). The role of EMT in human papilloma virus (HPV)-positive squamous cell carcinoma (SCC) is still not understood. The aim of this study was to investigate the expression pattern in p16-positive and -negative SCC cells of vimentin, β-catenin and E-cadherin after stimulation with growth factors. We incubated the p16-positive CERV196 and p16-negative HNSCC22B SCC cell lines with EGF and EGF/TGFβ1 (10 ng/ml) and detected E-cadherin, vimentin and β-catenin by immunocytochemistry and enzyme-linked immunosorbent assay after 5, 24 and 96 h. We found a low expression of vimentin in all studied tumor cell lines. The negative control of HNSCC22B cells showed a higher intrinsic level of membranous E-cadherin and β-catenin. We found statistically significant EGF/TGFβ1-induced expression of vimentin dependent on incubation time in p16-negative HNSCC22B cells. Particularly in the presence of EGF, we detected an increase of β-catenin and vimentin expression in p16-positive SCC tumor cell lines in addition to induced cell scattering and unexpected expression of E-cadherin. In conclusion, E-cadherin, β-catenin and vimentin expression are important features to characterize EMT-like events. We were able to show incomplete EGF-induced EMT with β-catenin expression in p16-positive SCC. Extended studies are required to investigate the mechanistic role of EMT markers, especially in p16-positive SCC, in order to develop new anti-SCC therapies to block EMT progression.