title: Chemotherapeutic alteration of β-catenin and c-kit expression by imatinib             in p16-positive squamous cell carcinoma compared to HPV-negative HNSCC cells in             vitro.
abstract: The most common neoplasm arising in the upper aerodigestive tract is head             and neck squamous cell carcinoma (HNSCC). Tumor growth, invasion and systemic             dissemination is a multistep process of dysregulated cellular signaling pathways             and an altered cell-cell and cell-matrix interaction. Aberrant Wnt/β-catenin signaling             is linked to tumor development and dissemination in several tumor entities. β-catenin             is a multifunctional protein within the canonical Wnt pathway, which is an important             factor for reducing cell-cell adhesion in malignant tissue and for triggering             cell cycle progression and unscheduled proliferation. Another pivotal factor in             carcinogenesis is the tyrosine kinase receptor c-kit, which in the case of dysregulated             expression is associated with neoplastic transformation in epithelial tissue.             This study evaluates the expression pattern of secreted and nuclear β-catenin             and c-kit in p16-positive and HPV-negative squamous cell carcinomas (SCC) and             the vulnerability of therapy with the tyrosine kinase inhibitor imatinib as a             potential targeted treatment modality compared to platinum-based chemotherapeutic             drugs. The different squamous tumor cell lines were incubated with increasing             concentrations of carboplatin (3 or 7.5 µmol/ml) and imatinib (18 or 30 µmol/ml).             ELISA and immunohistochemical methods were carried out after 48, 72, 120, 192             and 240 h. We detected a reliable trend towards significantly decreased cytosolic             and nuclear β-catenin and c-kit expression levels in p16-positive SCC and non-HPV             HNSCC cells induced by imatinib exposure for an extended incubation period, whereas             platinum-based agents had no or, at best, a slight influence. Virus-transformed             squamous cell carcinoma (CERV196) cells were characterized by a reduced susceptibility             to an imatinib-altered β-catenin expression. Further studies are planned to investigate             this observance in HPV-positive HNSCC in vitro. The implementation of a selective             molecular therapy in established chemotherapeutic regimes may enhance the efficacy             of platinum-based chemotherapy without increased toxicity and could thus improve             the clinical outcome in HNSCC, irrespective of the HPV status.
authors: Department of Otorhinolaryngology, Head and Neck Surgery, Medical Faculty of Mannheim, University of Heidelberg, Mannheim, Germany. johannes.schultz@umm.de
authors: J D
authors: JD
authors: Schultz
authors: J U
authors: JU
authors: Sommer
authors: S
authors: S
authors: Hoedt
authors: P
authors: P
authors: Erben
authors: R D
authors: RD
authors: Hofheinz
authors: A
authors: A
authors: Faber
authors: C
authors: C
authors: Thorn
authors: K
authors: K
authors: Hörmann
authors: A
authors: A
authors: Sauter
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001549:Benzamides; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000821:virology; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000821:virology; D006801:Humans; D000068877:Imatinib Mesylate; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D030361:Papillomavirus Infections / Q000150:complications / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D019089:Stem Cell Factor / Q000096:biosynthesis*; D014758:Viral Core Proteins / Q000378:metabolism; D051176:beta Catenin / Q000096:biosynthesis*
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D019089:Stem Cell Factor; D014758:Viral Core Proteins; D051176:beta Catenin; D000068877:Imatinib Mesylate