Development of Novel Murine BRAFV600E-Driven Papillary Thyroid Cancer Cell Lines for Modeling of Disease Progression and Preclinical Evaluation of Therapeutics

Grace Purvis Branigan; Victoria Casado-Medrano; Alison B. O’Neill; Julio C. Ricarte-Filho; Nicole Massoll; Madeleine Salwen; Zachary Spangler; Michele Scheerer; Edward K. Williamson; Andrew J. Bauer; Aime T. Franco

doi:10.3390/cancers15030879

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

Grace Purvis Branigan, Victoria Casado-Medrano, Alison B. O’Neill, Julio C. Ricarte-Filho, Nicole Massoll, Madeleine Salwen, Zachary Spangler, Michele Scheerer, Edward K. Williamson, Andrew J. Bauer, Aime T. Franco

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

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.

Original language	English (US)
Article number	879
Journal	Cancers
Volume	15
Issue number	3
DOIs	https://doi.org/10.3390/cancers15030879
State	Published - Feb 2023
Externally published	Yes

Keywords

BRAF
cell lines
mouse model
PTC
thyroid cancer

ASJC Scopus subject areas

Oncology
Cancer Research

Access to Document

10.3390/cancers15030879

Cite this

Branigan, G. P., Casado-Medrano, V., O’Neill, A. B., Ricarte-Filho, J. C., Massoll, N., Salwen, M., Spangler, Z., Scheerer, M., Williamson, E. K., Bauer, A. J., & Franco, A. T. (2023). Development of Novel Murine BRAF^V600E-Driven Papillary Thyroid Cancer Cell Lines for Modeling of Disease Progression and Preclinical Evaluation of Therapeutics. Cancers, 15(3), Article 879. https://doi.org/10.3390/cancers15030879

Branigan, GP, Casado-Medrano, V, O’Neill, AB, Ricarte-Filho, JC, Massoll, N, Salwen, M, Spangler, Z, Scheerer, M, Williamson, EK, Bauer, AJ & Franco, AT 2023, 'Development of Novel Murine BRAF^V600E-Driven Papillary Thyroid Cancer Cell Lines for Modeling of Disease Progression and Preclinical Evaluation of Therapeutics', Cancers, vol. 15, no. 3, 879. https://doi.org/10.3390/cancers15030879

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abstract = "The Cancer Genome Atlas study in thyroid cancer exposed the genomic landscape of ~500 PTCs and revealed BRAFV600E-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 BRAFV600E-driven papillary thyroid cancer (PTC) cell lines established from a BrafV600E+/−/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 BRAFV600E-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 BRAFV600E-driven PTC.",

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