Characterization of human follicular thyroid cancer cell lines in preclinical mouse models

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.

Preclinical Imaging for the Study of Mouse Models of Thyroid Cancer

“…While the xenograft models are quite straightforward in that the cells grown and collected are injected into the subcutaneous tissues of immunocompromised mice, the orthotopic model is more complex to establish, since it requires a microsurgical procedure to directly place the cells into one or both the thyroid lobes [ 32 , 33 , 34 ]. Nonetheless, since the development of such a model [ 35 ], orthotopic implantation has been widely adopted to study the genetic and bio-molecular patterns of thyroid carcinogenesis [ 9 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ].…”

“…Even if the orthotopic model closely resembles the original biological tumor’s behavior in term of local invasion and metastasis [ 35 , 36 , 37 , 40 ], particularly when aggressive ATC cells are used, other specific models have been developed to study metastasis [ 32 , 45 ]. Furthermore, in the orthotopic mouse models, the local invasion of neck tissues by the primary tumor can lead to animal suffering, due to the inability to swallow or breath properly; thus, there might not be enough time for the development of metastasis [ 39 , 40 ].…”

Cytotoxic and genotoxic effects of 131I and 60Co in follicular thyroid cancer cell (WRO) with and without recombinant human thyroid‐stimulating hormone treatment

“…In general, differentiated thyroid cancers (DTC), including PTC and FTC, tend to be biologically indolent, highly curable and has an excellent prognosis [Leonardi et al, ; Reeb et al, ]. The initial standard medical treatment for DTC after thyroidectomy is radioiodine ablation with (conventional therapy) or without thyroid hormone suppression therapy (use of recombinant human thyrotropin, rhTSH) [Pacini and Castagna, ; Zanotti‐Fregonara et al, ; da Silva et al, ].…”

“…The first characterization of WRO cell was documented by Estour et al [] who evaluated the effect of external radiation by 60 Co in a single dose of 10 Gy. Reeb et al [] demonstrated that they were the most tumorigenic and metastatic of the three human FTC cell lines (WRO, FTC‐238, TT 2609‐CO2) analyzed in xenotransplantation assays in immunodeficient mice.…”

“…The rhTSH used in this study was prepared in our laboratory and showed similar characteristics [Peroni et al, ; Mendonça et al, ; Oliveira et al, ; Damiani et al, ] and cytogenetic effects [da Silva et al, ] to Thyrogen, a widely applied commercial preparation from Genzyme Corporation (Framingham, MA). The choice of WRO cells as the object of this study is justified because this cell line presents peculiar characteristics: they belong to a cell line derived from FTC, less prevalent than PTC, but more metastatic and aggressive than PTC [Hua et al, ; Reeb et al, ]. Moreover, WRO cells harbor BRAF V600E mutation that occurs exclusively in PTC or PTC‐derived tumor [Xing, ].…”