Unexpected alteration of β-catenin and c-KIT expression by 5-FU and docetaxel in p16-positive squamous cell carcinoma compared to HPV-negative HNSCC cells in vitro

• Published in: Anticancer research Vol. 33; no. 6; pp. 2457 - 2465
• Main Authors: Umbreit, Claudia, Aderhold, Christoph, Faber, Anne, Sommer, Jörg Ulrich, Sauter, Alexander, Hofheinz, Ralf-Dieter, Stern-Sträter, Jens, Hoermann, Karl, Schultz, Johannes David
• Format: Journal Article
• Language: English
• Published: Greece 01.06.2013
• Subjects: Antimetabolites - therapeutic use; Antineoplastic Agents - therapeutic use; beta Catenin - biosynthesis; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - virology; Cell Line, Tumor; Enzyme-Linked Immunosorbent Assay; Fluorouracil - pharmacology; Fluorouracil - therapeutic use; Head and Neck Neoplasms - drug therapy; Head and Neck Neoplasms - metabolism; Head and Neck Neoplasms - virology; Human papillomavirus 16; Humans; Immunohistochemistry; Papillomavirus Infections - complications; Proto-Oncogene Proteins c-kit - biosynthesis; Signal Transduction - drug effects; Taxoids - pharmacology; Taxoids - therapeutic use; Wnt Signaling Pathway - drug effects; epithelial mesenchymal transition (EMT); human papillomavirus (HPV); β-catenin; c-KIT; docetaxel; protein tyrosine kinase; extracellular matrix; 5-FU; head and neck squamous cell carcinoma
• ISSN: 0250-7005; 1791-7530

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common type of cancer worldwide. In several tumour entities, the tyrosine kinase receptor c-KIT is associated with tumour transformation in the epithelial tissue in cases of aberrant expression. Furthermore, tumour development and dissemination are a result of dysregulated cellular pathways such as the WNT/β-catenin pathway. β-Catenin is a multifunctional protein within the canonical WNT signalling pathway and a pivotal factor for the stabilization of cell-cell interactions. In malignant tissues, β-catenin triggers tumour proliferation and progression. The aim of this study is to investigate the expression patterns of c-KIT and β-catenin in human papillomavirus-negative and p16-positive SCC and to evaluate the chemosensitivity of the tumour cells to the chemotherapeutical agents docetaxel and 5-fluorouracil (5-FU). We incubated the tumour cell lines with docetaxel (5 μmol/ml) and 5-FU (1 μmol/ml) and detected β-catenin and c-KIT by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) after 48, 72, 120, 192 and 240 h. We found a reliable trend towards decreased β-catenin expression levels in p16-positive and p16-negative tumour cell lines when incubated with docetaxel, in addition to induced apoptotic effect. At best, 5-FU had a slight influence on the alteration of the expression of β-catenin. Dose escalation of docetaxel and 5-FU had no statistically significant effect on the expression of β-catenin or c-KIT. In HPV-negative HNSCC, a reduced expression level of β-catenin and c-KIT was detected in an incubation period-dependent manner. p16-transformed SCC (CERV196) cells were characterized by a reduced susceptibility to docetaxel induced alteration of β-catenin expression. We were unable to confirm the clinically-substantiated increased chemosensitivity of p16-positive tumour cells in vitro. Extended studies and clinical trials are needed to investigate these findings further in HPV-associated HNSCC.