Targeting VEGFR and FGFR in head and neck squamous cell carcinoma in vitro
| Autor: | Valentin Steinacker, Alexander C. Kübler, Roman C. Brands, Francesco De Donno, Luise M. Knierim, Urs D.A. Müller-Richter, Axel Seher, Stefan Hartmann |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Oncology Cancer Research medicine.medical_specialty Indazoles Indoles Receptor expression Quinolones Biology Pazopanib 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor Internal medicine medicine Humans Protein Kinase Inhibitors Cell Proliferation Sulfonamides Tumor microenvironment Squamous Cell Carcinoma of Head and Neck Cell growth Receptor Protein-Tyrosine Kinases General Medicine Cell cycle medicine.disease Head and neck squamous-cell carcinoma stomatognathic diseases Pyrimidines Receptors Vascular Endothelial Growth Factor 030104 developmental biology chemistry Head and Neck Neoplasms 030220 oncology & carcinogenesis Carcinoma Squamous Cell Benzimidazoles Nintedanib Tyrosine kinase Signal Transduction medicine.drug |
| Zdroj: | Oncology Reports. 38:1877-1885 |
| ISSN: | 1791-2431 1021-335X |
| Popis: | Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease characterized by a tumor microenvironment (TME) that overexpresses vascular endothelial growth factor receptor (VEGFR) and fibroblast growth factor receptor (FGFR), which can lead to neovascularization, tumor growth and metastasis. Therapeutic strategies inhibiting these signaling pathways might lead to innovative HNSCC treatments. Five HNSCC cell lines were characterized based on VEGFR1-3 and FGFR1-4 expression by sqRT-PCR and treated with three different tyrosine kinase inhibitors (TKIs) (nintedanib, dovitinib and pazopanib), all of which are effective against VEGFR and FGFR family members. Crystal violet assays were performed to analyze the effect of the treatments on cell growth (viability). Additionally, VEGFR1-3 and FGFR1-4 expression data were retrieved from The Cancer Genome Atlas (TCGA), and statistical analyses were performed to investigate the receptor expression level in the different cell lines and the efficacy of the single-agent treatments. A correlation analysis was performed to quantify the degree of relationship between receptor expression and drug efficacy. With the exception of VEGFR2, the targeted receptors were expressed at different levels in all of the cell lines. The cell lines exhibited concentration-dependent responses with cell line-specific differences toward two of the three TKIs (nintedanib and dovitinib). Notably, all of the cell lines were resistant to pazopanib. TKIs have potential as therapeutic agents for HNSCC. Cell line-specific differences were observed in our in vitro experiments. The observed pazopanib resistance could be explained by receptor expression. Further investigation is required to determine TKI efficacy in HNSCC. |
| Databáze: | OpenAIRE |
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