Development of Novel Murine BRAF(V600E)-Driven Papillary Thyroid Cancer Cell Lines for Modeling of Disease Progression and Preclinical Evaluation of Therapeutics

SIMPLE SUMMARY: Laboratory experimental models are essential for advancements in thyroid cancer translational research. In this study, we discuss the development and characterization of six cell-based models of BRAF(V600E)-driven papillary thyroid cancer that closely mimic the heterogeneous pathological progression of the disease seen in patients despite sharing a common driver mutation. We anticipate that these newly developed models will allow for the discovery of novel mechanisms that determine differences in disease progression among BRAF(V600E)-driven thyroid cancers and facilitate the testing of therapeutic interventions. ABSTRACT: The Cancer Genome Atlas study in thyroid cancer exposed the genomic landscape of ~500 PTCs and revealed BRAF(V600E)-mutant tumors as having different prognosis, contrasting indolent cases and those with more invasive disease. Here, we describe the generation and characterization of six novel BRAF(V600E)-driven papillary thyroid cancer (PTC) cell lines established from a Braf(V600E)(+/−)/Pten(+/−)/TPO-Cre mouse model that spontaneously develop thyroid tumors. The novel cell lines were obtained from animals representing a range of developmental stages and both sexes, with the goal of establishing a heterogeneous panel of PTC cell lines sharing a common driver mutation. These cell lines recapitulate the genetics and diverse histopathological features of BRAF(V600E)-driven PTC, exhibiting differing degrees of growth, differentiation, and invasive potential that may help define mechanisms of pathogenesis underlying the heterogeneity present in the patient population. We demonstrate that these cell lines can be used for a variety of in vitro applications and can maintain the potential for in vivo transplantation into immunocompetent hosts. We believe that these novel cell lines will provide powerful tools for investigating the molecular basis of thyroid cancer progression and will lead to the development of more personalized diagnostic and treatment strategies for BRAF(V600E)-driven PTC.