KGFR as a possible therapeutic target in middle ear cholesteatoma

Abstract

Conclusion: We demonstrated that repression of keratinocyte growth factor (KGF) receptor (KGFR) could be a potentially useful strategy in the conservative treatment of middle ear cholesteatoma. Objectives: Recently, the use of a selective inhibitor of the KGFR, SU5402, in an in vitro experiment resulted in the inhibition of the differentiation and proliferation of epithelial cells through KGF secretion by fibroblasts isolated from the cholesteatoma. In this study, we investigated the effects of the KGFR inhibitor during middle ear cholesteatoma formation in vivo. Methods: Based on the role of KGF in the development of cholesteatoma, Flag-hKGF cDNA driven by CMV14 promoter was transfected through electroporation into the external auditory canal of rats five times on every fourth day. Ears transfected with empty vector were used as controls. KGFR selective inhibitor (SU5402) or MEK inhibitor (PD0325901) was administered in the right ear of five rats after vector transfection. In the control, 2% DMSO in PBS was administered in the other ears after vector transfection. Results: The use of a selective KGFR inhibitor, SU5402, completely prevented middle ear cholesteatoma formation in the rats.

Keywords::

• Keratinocyte growth factor
• KGF
• KGF receptor inhibitor
• in vivo model
• electroporation

Acknowledgments

The authors thank Dr. Jeffrey S. Rubin from the National Cancer Institute/CCR/LCMB, for providing the human KGF cDNA construct. The study was supported by a Grant-in-Aid for Scientific Research from the Japanese Ministry of Education, Science, Sports, and Culture (no. 23791906 to T.Y-F.) and by a grant from the Naito Foundation (to T.Y-F.).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.