Targeting VEGFR and FGFR in head and neck squamous cell carcinoma in vitro

Brands,Roman C.; Knierim,Luise M.; De Donno,Francesco; Steinacker,Valentin; Hartmann,Stefan; Seher,Axel; Kübler,Alexander C.; Müller-Richter,Urs D.A.

doi:10.3892/or.2017.5801

Targeting VEGFR and FGFR in head and neck squamous cell carcinoma in vitro

Authors:
- Roman C. Brands
- Luise M. Knierim
- Francesco De Donno
- Valentin Steinacker
- Stefan Hartmann
- Axel Seher
- Alexander C. Kübler
- Urs D.A. Müller-Richter
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Affiliations: Department of Oral and Maxillofacial Plastic Surgery, University Hospital Würzburg, D-97070 Würzburg, Germany
Published online on: July 10, 2017 https://doi.org/10.3892/or.2017.5801
Pages: 1877-1885

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Abstract

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.

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