Effect of small molecule tyrosine kinase inhibitors on TGFß1-expression in HPV-positive and -negative HNSCC

Introduction The role of transforming growth factor beta (TGFß) in the context of malignant neoplasia is complex. TGFß functions as a tumor promoter in advanced tumor stages of malignant head and neck squamous cell tumors (HNSCC). In this study, we investigated the effect of selective tyrosine kinase inhibitors (TKIs) on the expression of TGFß1 in vitro in HPV-positive and -negative squamous cell carcinoma cells.

Material and Methods Two human HPV-negative cell lines (UMSCC-11A/-14C) and one HPV-positive cell line (CERV96) were used. Nilotinib, dasatinib, gefitinib, erlotinib and everolimus (20 μmol/l each) were incubated with the tumor cells for 24-96h. Cell proliferation was measured by proliferation assay and protein concentration of TGFß1 by sandwich ELISA. Untreated cells were used as negative control.

Results TGFß1 was expressed in all cell lines, with the lowest expression level shown in HPV+ CERV196 cells. The TKIs resulted in significant changes in the expression levels of TGFß1 in the different cell lines compared with the negative control. Here, the expression of the ligand showed a downward trend, with the greatest effect among the EGFR inhibitors in the UMSCC 11A cell line.

Discussion TGFß1 is shown to be overexpressed in HNSCC. Our results show that selective TKIs can significantly reduce the expression levels of TGFß1. Currently, the exact molecular mechanisms are not fully understood. However, the results lead to a better understanding of tumor biology in relation to TGFß1 and its interaction with selective TKIs. Selective inhibition of TGFß1 in combination with existing TKIs could therefore be a promising approach for further studies.

Publication History

Article published online:
12 May 2023