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

  • Authors:
    • J. D. Schultz
    • J. U. Sommer
    • S. Hoedt
    • P. Erben
    • R. D. Hofheinz
    • A. Faber
    • C. Thorn
    • K. Hörmann
    • A. Sauter
  • View Affiliations

  • Published online on: October 12, 2011     https://doi.org/10.3892/or.2011.1499
  • Pages: 270-280
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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.

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January 2012
Volume 27 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Schultz JD, Sommer JU, Hoedt S, Erben P, Hofheinz RD, Faber A, Thorn C, Hörmann K and Sauter A: 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. Oncol Rep 27: 270-280, 2012.
APA
Schultz, J.D., Sommer, J.U., Hoedt, S., Erben, P., Hofheinz, R.D., Faber, A. ... Sauter, A. (2012). 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. Oncology Reports, 27, 270-280. https://doi.org/10.3892/or.2011.1499
MLA
Schultz, J. D., Sommer, J. U., Hoedt, S., Erben, P., Hofheinz, R. D., Faber, A., Thorn, C., Hörmann, K., Sauter, A."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". Oncology Reports 27.1 (2012): 270-280.
Chicago
Schultz, J. D., Sommer, J. U., Hoedt, S., Erben, P., Hofheinz, R. D., Faber, A., Thorn, C., Hörmann, K., Sauter, A."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". Oncology Reports 27, no. 1 (2012): 270-280. https://doi.org/10.3892/or.2011.1499