A Novel External Auditory Canal Squamous Cell Carcinoma Cell Line Sensitive to CDK4/6 Inhibition.

ABSTRACT

OBJECTIVE: To characterize cell line CAE606 derived from a squamous cell carcinoma (SCC) of the external auditory canal (EAC) and to show its usefulness as a model for testing candidate therapeutic agents. STUDY DESIGN: Preclinical translational research. SETTING: Biomedical research institute. METHODS: The cell line was initiated from a moderately differentiated T2N0M0 EAC SCC. We studied its histologic and genetic features as well as growth and invasion parameters. Sensitivity to cell CDK4/6 cell cycle inhibitor palbociclib was analyzed. RESULTS: CAE606 cells expressed heavy molecular weight cytokeratin, p63, and vimentin. The population doubling time was 25.8 hours, and the cells showed fast collective cell migration in a wound-healing assay. Short tandem repeat analysis confirmed it to be derived from the primary tumor of the patient. Next-generation sequencing revealed alterations in cell cycle regulation genes, including inactivating mutations in CDKN2A and TP53 and high-level amplification of CCND1 and EGFR. CAE606 showed a strong decrease of phospo-Rb expression upon exposure to the CDK4/6 inhibitor palbociclib, causing significant growth inhibition with an IC50 of 0.46 µM. CONCLUSION: This is the first report of a stable EAC SCC cell line. Its genetic features make it a useful tool for preclinical testing of new therapeutic agents for EAC SCC, particularly those targeting cell cycle regulation in combination with radio- and chemotherapy or other specific signaling pathway inhibitors.