Potential Utility and Limitations of Thyroid Cancer Cell Lines as Models for Studying Thyroid Cancer

Pilli, Tania; Prasad, Kartik; Jayarama, Shankar; Pacini, Furio; Prabhakar, Bellur S.

doi:10.1089/thy.2009.0195

Cited by 70 publications

(54 citation statements)

References 70 publications

(109 reference statements)

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“…In this study, B2311-mediated inhibition of Akt phosphorylation upregulated the expression of NIS, but it markedly downregulated that of the TSHR gene, which suggests that expression of the latter gene -at least in this cell line -may be associated with the activation of growthpromoting signals. The findings regarding the TSHR are limited to only one cell line investigated, FTC-133, and could not be reproduced in other cell lines, because most of them show loss of TSHR expression (Pilli et al 2009;Sponziello M, Durante C, Russo D & Filetti S, 2013, unpublished observations), probably as a result of the cells' adaptation to in vitro growth conditions (Van Staveren et al 2007). However, the NIS/TSHR expression pattern of FTC-133 resembles that observed in thyroid cancer cells in vivo, where TSHR expression is often preserved or only mildly decreased.…”

Section: Discussionmentioning

confidence: 94%

“…Few data are available on the molecular mechanisms underlying the regulation of TSHR expression in thyroid cancer cells. Indeed, at variance with the reports in tumor tissues, loss of TSHR expression has been described in most of human thyroid cancer cells (Pilli et al 2009; Sponziello M, Durante C, Russo D & Filetti S, 2013, unpublished observations). However, hypermethylation of the TSHR promoter has been documented in a series of thyroid cancer tissues (Xing et al 2003).…”

Section: Introductionmentioning

confidence: 87%

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Different expression of TSH receptor and NIS genes in thyroid cancer: role of epigenetics

D’Agostino¹,

Sponziello²,

Puppin³

et al. 2013

Journal of Molecular Endocrinology

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The TSH receptor (TSHR) and sodium/iodide symporter (NIS) are key players in radioiodinebased treatment of differentiated thyroid cancers. While NIS (SLC5AS) expression is diminished/lost in most thyroid tumors, TSHR is usually preserved. To examine the mechanisms that regulate the expression of NIS and TSHR genes in thyroid tumor cells, we analyzed their expression after inhibition of ras-BRAF-MAPK and PI3K-Akt-mTOR pathways and the epigenetic control occurring at the gene promoter level in four human thyroid cancer cell lines. Quantitative real-time PCR was used to measure NIS and TSHR mRNA in thyroid cancer cell lines (TPC-1, BCPAP, WRO, and FTC-133). Western blotting was used to assess the levels of total and phosphorylated ERK and Akt. Chromatin immunoprecipitation was performed for investigating histone post-translational modifications of the TSHR and NIS genes. ERK and Akt inhibitors elicited different responses of the cells in terms of TSHR and NIS mRNA levels. Akt inhibition increased NIS transcript levels and reduced those of TSHR in FTC-133 cells but had no significant effects in BCPAP. ERK inhibition increased the expression of both genes in BCPAP cells but had no effects in FTC-133. Histone posttranslational modifications observed in the basal state of the four cell lines as well as in BCPAP treated with ERK inhibitor and FTC-133 treated with Akt inhibitor show cell-and gene-specific differences. In conclusion, our data indicate that in thyroid cancer cells the expression of TSHR and NIS genes is differently controlled by multiple mechanisms, including epigenetic events elicited by major signaling pathways involved in thyroid tumorigenesis.

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 87%

Different expression of TSH receptor and NIS genes in thyroid cancer: role of epigenetics

D’Agostino¹,

Sponziello²,

Puppin³

et al. 2013

Journal of Molecular Endocrinology

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“…Several independent analyses of commonly studied thyroid cancer cell lines confirm that these cell lines have largely ceased to express markers of thyrocyte differentiation, and more closely represent anaplastic thyroid cancers than DTC (Meireles et al 2007, van Staveren et al 2007, Pilli et al 2009). This is particularly true of TSHR expression, which is downregulated early in monolayer culture due to disruption of follicular architecture and loss of apical-basal polarity (Williams & Wynford-Thomas 1997).…”

Section: Tshr Expression In In Vitro Models Of Thyroid Cancermentioning

confidence: 95%

“…This is particularly true of TSHR expression, which is downregulated early in monolayer culture due to disruption of follicular architecture and loss of apical-basal polarity (Williams & Wynford-Thomas 1997). In a recent review, Pilli and coworkers (Pilli et al 2009) note that TSHR expression was not detected in any of a number of commonly studied cell lines. There are conflicting data regarding TSHR expression in the FTC-133 cell line (originating from a lymph node metastases of a differentiated human follicular thyroid cancer), with some authors demonstrating mRNA expression (D'Agostino et al 2014) and TSH ligand binding (Paolino et al 2014), which may represent heterogeneity within this cell line between laboratories.…”

Section: Tshr Expression In In Vitro Models Of Thyroid Cancermentioning

confidence: 99%

“…There are conflicting data regarding TSHR expression in the FTC-133 cell line (originating from a lymph node metastases of a differentiated human follicular thyroid cancer), with some authors demonstrating mRNA expression (D'Agostino et al 2014) and TSH ligand binding (Paolino et al 2014), which may represent heterogeneity within this cell line between laboratories. Additionally, there is conflicting evidence for TSHR expression in the BCPAP cell line (derived from a poorly differentiated PTC) (Pilli et al 2009, D'Agostino et al 2014, Dotan et al 2016. Similarly, PTC cells grown in thyrosphere culture lack expression of thyroid-specific proteins, and cells fail to produce cAMP in response to TSH stimulation , Giani et al 2015.…”

Section: Tshr Expression In In Vitro Models Of Thyroid Cancermentioning

confidence: 99%

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Targeting the TSH receptor in thyroid cancer

Rowe¹,

Paul²,

Gedye³

et al. 2017

Endocrine-Related Cancer

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Recent advances in the arena of theranostics have necessitated a re-examining of previously established fields. The existing paradigm of therapeutic thyroid-stimulating hormone receptor (TSHR) targeting in the post-surgical management of differentiated thyroid cancer using levothyroxine and recombinant human thyroid-stimulating hormone (TSH) is well understood. However, in an era of personalized medicine, and with an increasing awareness of the risk profile of longstanding pharmacological hyperthyroidism, it is imperative clinicians understand the molecular basis and magnitude of benefit for individual patients. Furthermore, TSHR has been recently re-conceived as a selective target for residual metastatic thyroid cancer, with pilot data demonstrating effective targeting of nanoparticles to thyroid cancers using this receptor as a target. This review examines the evidence for TSHR signaling as an oncogenic pathway and assesses the evidence for ongoing TSHR expression in thyroid cancer metastases. Priorities for further research are highlighted.

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In vitro antitumoral effects of the steroid ouabain on human thyroid papillary carcinoma cell lines

Teixeira

Passos

Haddad

et al. 2021

Environmental Toxicology

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Ouabain is a steroid described as a compound extracted from plants that is capable of binding to Na+, K+‐ATPase, inhibiting ion transport and triggering cell signaling pathways. Due to its positive ionotropic effect, ouabain was used for more than 200 years for the treatment of cardiac dysfunctions. Numerous antitumor effects of ouabain have been described so far; however, its role on thyroid cancer is still poorly understood. Therefore, the aim of the present work was to evaluate the effect of ouabain on the biology of human papillary thyroid cancer cells. For this, three human thyroid cell lines were used: NTHY‐ori, a non‐tumor lineage, BCPAP and TPC‐1, both derived from papillary carcinomas. Cells were cultured in the presence or absence of ouabain. Subsequently, we evaluated its effects on the viability, cell death, cell cycle, and migratory ability of these cell lines. We also investigated the impact of ouabain in IL‐6/IL‐6R and epithelial to mesenchymal transition markers expression. Our results indicate that ouabain (10−7 M), decreased the number of NTHY‐ori, TPC‐1 and BCPAP viable cells and induced cell cycle arrest after in vitro culture, but did not appear to promote cell death. In TPC‐1 cells ouabain also inhibited cell migration; increased IL‐6/IL‐6R expression and IL‐6 secretion; and diminished vimentin and SNAIL‐1 expression. Collectively, our results indicate that ouabain has an antitumoral role on human papillary thyroid carcinomas in vitro. Even though additional studies are necessary, our work contributes to the discussion of the possibility of new clinical trials of ouabain.

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Potential Utility and Limitations of Thyroid Cancer Cell Lines as Models for Studying Thyroid Cancer

Cited by 70 publications

References 70 publications

Different expression of TSH receptor and NIS genes in thyroid cancer: role of epigenetics

Different expression of TSH receptor and NIS genes in thyroid cancer: role of epigenetics

Targeting the TSH receptor in thyroid cancer

In vitro antitumoral effects of the steroid ouabain on human thyroid papillary carcinoma cell lines

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