Abstract

Follicular thyroid cancer (FTC) is the second most common type of thyroid cancers. In order to develop more effective personalized therapies, it is necessary to thoroughly evaluate patient-derived cell lines in in vivo preclinical models before using them to test new, targeted therapies. This study evaluates the tumorigenic and metastatic potential of a panel of three human FTC cell lines (WRO, FTC-238, and TT1609-CO2) with defined genetic mutations in two in vivo murine models: an orthotopic thyroid cancer model to study tumor progression and a tail vein injection model to study metastasis. All cell lines developed tumors in the orthotopic model, with take rates of 100%. Notably, WRO-derived tumors grew two to four times faster than tumors arising from the FTC-238 and TT2609-CO2 cell lines. These results mirrored those of a tail vein injection model for lung metastasis: one hundred percent of mice injected with WRO cells in the tail vein exhibited aggressive growth of bilateral lung metastases within 35 days. In contrast, tail vein injection of FTC-238 or TT2609-CO2 cells did not result in lung metastasis. Together, our work demonstrates that these human FTC cell lines display highly varied tumorigenic and metastatic potential in vivo with WRO being the most aggressive cell line in both orthotopic and lung metastasis models. This information will be valuable when selecting cell lines for preclinical drug testing.

Highlights

  • Follicular thyroid cancer (FTC) is the second most frequently diagnosed thyroid cancer after papillary thyroid cancer (PTC)

  • We found that FTC-238 and WRO express PAX8, a thyroid transcription factor, whereas TT2609-CO2 expresses thyroid transcription factor 1 (TTF1)

  • The aim of this study was to assess a panel of three human FTC cell lines for their tumorigenic and metastatic potential in xenotransplantation assays in immunodeficient mice

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Summary

Introduction

Follicular thyroid cancer (FTC) is the second most frequently diagnosed thyroid cancer after papillary thyroid cancer (PTC). About 10,000 cases of FTC are diagnosed annually in the United States, comprising about 10–15% of all thyroid cancer cases. More research is needed to determine the cause of the disease; to study tumor initiation, progression, and drug resistance; and to eventually develop new and improved drugs for this group of patients. Human cell lines derived from tumors removed from thyroid cancer patients provide a useful model of thyroid disease mechanisms. Defined cell lines with known driver mutations are useful for clinicians and researchers striving to develop a more personalized approach to thyroid cancer therapy.

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