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

Autor: García-Marín R; Department of Head and Neck Cancer, Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo, Spain., Cabal VN; Department of Head and Neck Cancer, Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo, Spain., Fernández-Cedrón Bermejo C; Department of Otolaryngology, Hospital Universitario Central de Asturias, Oviedo, Spain., Riobello C; Department of Head and Neck Cancer, Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo, Spain., Suárez-Fernández L; Department of Head and Neck Cancer, Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo, Spain., Codina-Martínez H; Department of Head and Neck Cancer, Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo, Spain., Navarro-García A; Department of Head and Neck Cancer, Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo, Spain., Lorenzo-Guerra SL; Department of Head and Neck Cancer, Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo, Spain., García-Martínez J; Department of Pediatric Hematology and Oncology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación Sanitaria La Princesa, Madrid, Spain., Vivanco B; Department of Pathology, Hospital Universitario Central de Asturias, Oviedo, Spain., López F; Department of Otolaryngology, Hospital Universitario Central de Asturias, Oviedo, Spain., Llorente JL; Department of Otolaryngology, Hospital Universitario Central de Asturias, Oviedo, Spain., Hermsen MA; Department of Head and Neck Cancer, Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo, Spain.
Jazyk: angličtina
Zdroj: Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery [Otolaryngol Head Neck Surg] 2023 Apr; Vol. 168 (4), pp. 729-737. Date of Electronic Publication: 2023 Feb 05.
DOI: 10.1177/01945998221089186
Abstrakt: 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 IC 50 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.
(© 2022 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)
Databáze: MEDLINE
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