Development of Novel Follicular Thyroid Cancer Models Which Progress to Poorly Differentiated and Anaplastic Thyroid Cancer

SIMPLE SUMMARY: Advancements in thyroid cancer are dependent on the availability of experimental models allowing for investigation in the laboratory setting. Here, we detail the development and characterization of three cell-based models of follicular thyroid cancer that closely mimic the genetic and pathological progression of the disease seen in patients, including progression to poorly differentiated and anaplastic thyroid cancer in some cases. We anticipate that these newly developed models will allow for the discovery of novel mechanisms of disease progression and the testing of therapeutic interventions. ABSTRACT: Recent developments in thyroid cancer research have been hindered by a lack of validated in vitro models, allowing for preclinical experimentation and the screening of prospective therapeutics. The goal of this work is to develop and characterize three novel follicular thyroid cancer (FTC) cell lines developed from relevant animal models. These cell lines recapitulate the genetics and histopathological features of FTC, as well as progression to a poorly differentiated state. We demonstrate that these cell lines can be used for a variety of in vitro applications and maintain the potential for in vivo transplantation into immunocompetent hosts. Further, cell lines exhibit differing degrees of dysregulated growth and invasive behavior that may help define mechanisms of pathogenesis underlying the heterogeneity present in the patient population. We believe these novel cell lines will provide powerful tools for investigating the molecular basis of thyroid cancer progression and lead to the development of more personalized diagnostic and treatment strategies.