Endocrinol Metab.  2022 Dec;37(6):830-838. 10.3803/EnM.2022.1636.

Preclinical Models of Follicular Cell-Derived Thyroid Cancer: An Overview from Cancer Cell Lines to Mouse Models

Affiliations
  • 1Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
  • 2Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA

Abstract

The overall prognosis of thyroid cancer is excellent, but some patients have grossly invasive disease and distant metastases with limited responses to systemic therapies. Thus, relevant preclinical models are needed to investigate thyroid cancer biology and novel treatments. Different preclinical models have recently emerged with advances in thyroid cancer genetics, mouse modeling and new cell lines. Choosing the appropriate model according to the research question is crucial to studying thyroid cancer. This review will discuss the current preclinical models frequently used in thyroid cancer research, from cell lines to mouse models, and future perspectives on patient-derived and humanized preclinical models in this field.

Keyword

Thyroid neoplasm; Cell line; Models, animal; Animals, genetically modified

Reference

1. Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid. 2016; 26:1–133.
Article
2. Landa I, Knauf JA. Mouse models as a tool for understanding progression in BrafV600E-driven thyroid cancers. Endocrinol Metab (Seoul). 2019; 34:11–22.
Article
3. Bible KC, Kebebew E, Brierley J, Brito JP, Cabanillas ME, Clark TJ, et al. 2021 American Thyroid Association guidelines for management of patients with anaplastic thyroid cancer. Thyroid. 2021; 31:337–86.
Article
4. Brose MS, Nutting CM, Jarzab B, Elisei R, Siena S, Bastholt L, et al. Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial. Lancet. 2014; 384:319–28.
Article
5. Schlumberger M, Tahara M, Wirth LJ, Robinson B, Brose MS, Elisei R, et al. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med. 2015; 372:621–30.
Article
6. Gianoukakis AG, Dutcus CE, Batty N, Guo M, Baig M. Prolonged duration of response in lenvatinib responders with thyroid cancer. Endocr Relat Cancer. 2018; 25:699–704.
Article
7. Subbiah V, Kreitman RJ, Wainberg ZA, Cho JY, Schellens JH, Soria JC, et al. Dabrafenib and trametinib treatment in patients with locally advanced or metastatic BRAF V600- mutant anaplastic thyroid cancer. J Clin Oncol. 2018; 36:7–13.
Article
8. Karapanou O, Simeakis G, Vlassopoulou B, Alevizaki M, Saltiki K. Advanced RAI-refractory thyroid cancer: an update on treatment perspectives. Endocr Relat Cancer. 2022; 29:R57–66.
Article
9. Chintakuntlawar AV, Yin J, Foote RL, Kasperbauer JL, Rivera M, Asmus E, et al. A phase 2 study of pembrolizumab combined with chemoradiotherapy as initial treatment for anaplastic thyroid cancer. Thyroid. 2019; 29:1615–22.
Article
10. Capdevila J, Wirth LJ, Ernst T, Ponce Aix S, Lin CC, Ramlau R, et al. PD-1 blockade in anaplastic thyroid carcinoma. J Clin Oncol. 2020; 38:2620–7.
Article
11. Mehnert JM, Varga A, Brose MS, Aggarwal RR, Lin CC, Prawira A, et al. Safety and antitumor activity of the antiPD-1 antibody pembrolizumab in patients with advanced, PD-L1-positive papillary or follicular thyroid cancer. BMC Cancer. 2019; 19:196.
Article
12. Haugen B, French J, Worden FP, Konda B, Sherman EJ, Dadu R, et al. Lenvatinib plus pembrolizumab combination therapy in patients with radioiodine-refractory (RAIR), progressive differentiated thyroid cancer (DTC): results of a multicenter phase II international thyroid oncology group trial. J Clin Oncol. 2020; 38(15 suppl):6512.
Article
13. Landa I, Ibrahimpasic T, Boucai L, Sinha R, Knauf JA, Shah RH, et al. Genomic and transcriptomic hallmarks of poorly differentiated and anaplastic thyroid cancers. J Clin Invest. 2016; 126:1052–66.
Article
14. Pozdeyev N, Gay LM, Sokol ES, Hartmaier R, Deaver KE, Davis S, et al. Genetic analysis of 779 advanced differentiated and anaplastic thyroid cancers. Clin Cancer Res. 2018; 24:3059–68.
Article
15. Landa I, Pozdeyev N, Korch C, Marlow LA, Smallridge RC, Copland JA, et al. Comprehensive genetic characterization of human thyroid cancer cell lines: a validated panel for preclinical studies. Clin Cancer Res. 2019; 25:3141–51.
Article
16. Schweppe RE, Klopper JP, Korch C, Pugazhenthi U, Benezra M, Knauf JA, et al. Deoxyribonucleic acid profiling analysis of 40 human thyroid cancer cell lines reveals crosscontamination resulting in cell line redundancy and misidentification. J Clin Endocrinol Metab. 2008; 93:4331–41.
Article
17. Gillet JP, Varma S, Gottesman MM. The clinical relevance of cancer cell lines. J Natl Cancer Inst. 2013; 105:452–8.
Article
18. Henderson YC, Ahn SH, Ryu J, Chen Y, Williams MD, ElNaggar AK, et al. Development and characterization of six new human papillary thyroid carcinoma cell lines. J Clin Endocrinol Metab. 2015; 100:E243–52.
Article
19. Maniakas A, Henderson YC, Hei H, Peng S, Chen Y, Jiang Y, et al. Novel anaplastic thyroid cancer PDXs and cell lines: expanding preclinical models of genetic diversity. J Clin Endocrinol Metab. 2021; 106:e4652–65.
Article
20. Chen D, Tan Y, Li Z, Li W, Yu L, Chen W, et al. Organoid cultures derived from patients with papillary thyroid cancer. J Clin Endocrinol Metab. 2021; 106:1410–26.
Article
21. Gu CY, Lee TK. Preclinical mouse models of hepatocellular carcinoma: an overview and update. Exp Cell Res. 2022; 412:113042.
Article
22. Nucera C, Nehs MA, Mekel M, Zhang X, Hodin R, Lawler J, et al. A novel orthotopic mouse model of human anaplastic thyroid carcinoma. Thyroid. 2009; 19:1077–84.
Article
23. Davis SN, Haugen BR. Ultrasound-guided orthotopic injections of thyroid cancer cell lines in mice. VideoEndocrinology. 2020; 7:ve.2020.0185.
Article
24. Kirschner LS, Qamri Z, Kari S, Ashtekar A. Mouse models of thyroid cancer: a 2015 update. Mol Cell Endocrinol. 2016; 421:18–27.
Article
25. Antonello ZA, Nucera C. Orthotopic mouse models for the preclinical and translational study of targeted therapies against metastatic human thyroid carcinoma with BRAF(V600E) or wild-type BRAF. Oncogene. 2014; 33:5397–404.
Article
26. Jin Y, Liu M, Sa R, Fu H, Cheng L, Chen L. Mouse models of thyroid cancer: bridging pathogenesis and novel therapeutics. Cancer Lett. 2020; 469:35–53.
Article
27. Zhang L, Gaskins K, Yu Z, Xiong Y, Merino MJ, Kebebew E. An in vivo mouse model of metastatic human thyroid cancer. Thyroid. 2014; 24:695–704.
Article
28. Morrison JA, Pike LA, Lund G, Zhou Q, Kessler BE, Bauerle KT, et al. Characterization of thyroid cancer cell lines in murine orthotopic and intracardiac metastasis models. Horm Cancer. 2015; 6:87–99.
Article
29. Henderson YC, Mohamed AS, Maniakas A, Chen Y, Powell RT, Peng S, et al. A high-throughput approach to identify effective systemic agents for the treatment of anaplastic thyroid carcinoma. J Clin Endocrinol Metab. 2021; 106:2962–78.
Article
30. Vanden Borre P, McFadden DG, Gunda V, Sadow PM, Varmeh S, Bernasconi M, et al. The next generation of orthotopic thyroid cancer models: immunocompetent orthotopic mouse models of BRAF V600E-positive papillary and anaplastic thyroid carcinoma. Thyroid. 2014; 24:705–14.
Article
31. Caperton CO, Jolly LA, Massoll N, Bauer AJ, Franco AT. Development of novel follicular thyroid cancer models which progress to poorly differentiated and anaplastic thyroid cancer. Cancers (Basel). 2021; 13:1094.
Article
32. Gunda V, Gigliotti B, Ashry T, Ndishabandi D, McCarthy M, Zhou Z, et al. Anti-PD-1/PD-L1 therapy augments lenvatinib’s efficacy by favorably altering the immune microenvironment of murine anaplastic thyroid cancer. Int J Cancer. 2019; 144:2266–78.
Article
33. Bertol BC, Bales ES, Calhoun JD, Mayberry A, Ledezma ML, Sams SB, et al. Lenvatinib plus anti-PD-1 combination therapy for advanced cancers: defining mechanisms of resistance in an inducible transgenic model of thyroid cancer. Thyroid. 2022; 32:153–63.
Article
34. Kim H, Kim M, Im SK, Fang S. Mouse Cre-LoxP system: general principles to determine tissue-specific roles of target genes. Lab Anim Res. 2018; 34:147–59.
Article
35. Kim CS, Zhu X. Lessons from mouse models of thyroid cancer. Thyroid. 2009; 19:1317–31.
Article
36. Knauf JA, Ma X, Smith EP, Zhang L, Mitsutake N, Liao XH, et al. Targeted expression of BRAFV600E in thyroid cells of transgenic mice results in papillary thyroid cancers that undergo dedifferentiation. Cancer Res. 2005; 65:4238–45.
Article
37. Charles RP, Iezza G, Amendola E, Dankort D, McMahon M. Mutationally activated BRAF(V600E) elicits papillary thyroid cancer in the adult mouse. Cancer Res. 2011; 71:3863–71.
Article
38. Chakravarty D, Santos E, Ryder M, Knauf JA, Liao XH, West BL, et al. Small-molecule MAPK inhibitors restore radioiodine incorporation in mouse thyroid cancers with conditional BRAF activation. J Clin Invest. 2011; 121:4700–11.
Article
39. Ho AL, Grewal RK, Leboeuf R, Sherman EJ, Pfister DG, Deandreis D, et al. Selumetinib-enhanced radioiodine uptake in advanced thyroid cancer. N Engl J Med. 2013; 368:623–32.
Article
40. Iravani A, Solomon B, Pattison DA, Jackson P, Ravi Kumar A, Kong G, et al. Mitogen-activated protein kinase pathway inhibition for redifferentiation of radioiodine refractory differentiated thyroid cancer: an evolving protocol. Thyroid. 2019; 29:1634–45.
Article
41. Franco AT, Malaguarnera R, Refetoff S, Liao XH, Lundsmith E, Kimura S, et al. Thyrotrophin receptor signaling dependence of Braf-induced thyroid tumor initiation in mice. Proc Natl Acad Sci U S A. 2011; 108:1615–20.
Article
42. McFadden DG, Vernon A, Santiago PM, Martinez-McFaline R, Bhutkar A, Crowley DM, et al. p53 constrains progression to anaplastic thyroid carcinoma in a Braf-mutant mouse model of papillary thyroid cancer. Proc Natl Acad Sci U S A. 2014; 111:E1600–9.
43. Charles RP, Silva J, Iezza G, Phillips WA, McMahon M. Activating BRAF and PIK3CA mutations cooperate to promote anaplastic thyroid carcinogenesis. Mol Cancer Res. 2014; 12:979–86.
Article
44. Santoro M, Melillo RM, Fusco A. RET/PTC activation in papillary thyroid carcinoma: European Journal of Endocrinology prize lecture. Eur J Endocrinol. 2006; 155:645–53.
Article
45. Greco A, Miranda C, Pierotti MA. Rearrangements of NTRK1 gene in papillary thyroid carcinoma. Mol Cell Endocrinol. 2010; 321:44–9.
Article
46. Jhiang SM, Sagartz JE, Tong Q, Parker-Thornburg J, Capen CC, Cho JY, et al. Targeted expression of the ret/PTC1 oncogene induces papillary thyroid carcinomas. Endocrinology. 1996; 137:375–8.
Article
47. Jhiang SM, Cho JY, Furminger TL, Sagartz JE, Tong Q, Capen CC, et al. Thyroid carcinomas in RET/PTC transgenic mice. Recent Results Cancer Res. 1998; 154:265–70.
Article
48. Powell DJ, Russell J, Nibu K, Li G, Rhee E, Liao M, et al. The RET/PTC3 oncogene: metastatic solid-type papillary carcinomas in murine thyroids. Cancer Res. 1998; 58:5523–8.
49. Buckwalter TL, Venkateswaran A, Lavender M, La Perle KM, Cho JY, Robinson ML, et al. The roles of phosphotyrosines-294, -404, and -451 in RET/PTC1-induced thyroid tumor formation. Oncogene. 2002; 21:8166–72.
Article
50. Russell JP, Powell DJ, Cunnane M, Greco A, Portella G, Santoro M, et al. The TRK-T1 fusion protein induces neoplastic transformation of thyroid epithelium. Oncogene. 2000; 19:5729–35.
Article
51. Santelli G, de Franciscis V, Portella G, Chiappetta G, D’Alessio A, Califano D, et al. Production of transgenic mice expressing the Ki-ras oncogene under the control of a thyroglobulin promoter. Cancer Res. 1993; 53:5523–7.
52. Vitagliano D, Portella G, Troncone G, Francione A, Rossi C, Bruno A, et al. Thyroid targeting of the N-ras(Gln61Lys) oncogene in transgenic mice results in follicular tumors that progress to poorly differentiated carcinomas. Oncogene. 2006; 25:5467–74.
Article
53. Miller KA, Yeager N, Baker K, Liao XH, Refetoff S, Di Cristofano A. Oncogenic Kras requires simultaneous PI3K signaling to induce ERK activation and transform thyroid epithelial cells in vivo. Cancer Res. 2009; 69:3689–94.
54. Pringle DR, Vasko VV, Yu L, Manchanda PK, Lee AA, Zhang X, et al. Follicular thyroid cancers demonstrate dual activation of PKA and mTOR as modeled by thyroid-specific deletion of Prkar1a and Pten in mice. J Clin Endocrinol Metab. 2014; 99:E804–12.
55. Jolly LA, Massoll N, Franco AT. Immune suppression mediated by myeloid and lymphoid derived immune cells in the tumor microenvironment facilitates progression of thyroid cancers driven by HrasG12V and Pten loss. J Clin Cell Immunol. 2016; 7:451.
Article
56. Kato Y, Ying H, Willingham MC, Cheng SY. A tumor suppressor role for thyroid hormone beta receptor in a mouse model of thyroid carcinogenesis. Endocrinology. 2004; 145:4430–8.
57. Furuya F, Lu C, Willingham MC, Cheng SY. Inhibition of phosphatidylinositol 3-kinase delays tumor progression and blocks metastatic spread in a mouse model of thyroid cancer. Carcinogenesis. 2007; 28:2451–8.
58. Yin L, Wang XJ, Chen DX, Liu XN, Wang XJ. Humanized mouse model: a review on preclinical applications for cancer immunotherapy. Am J Cancer Res. 2020; 10:4568–84.
Full Text Links
  • ENM
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr