Development of Novel Follicular Thyroid Cancer Models Which Progress to Poorly Differentiated and Anaplastic Thyroid Cancer.

Development of Novel Follicular Thyroid Cancer Models Which Progress to Poorly Differentiated and Anaplastic Thyroid Cancer.
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DOI:
10.3390/cancers13051094
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发表时间:
2021-03-04
期刊:
影响因子:
5.2
通讯作者:
Franco AT
Franco AT
中科院分区:
医学2区
文献类型:
--
作者:
Caperton CO;Jolly LA;Massoll N;Bauer AJ;Franco AT

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甲状腺癌的进展依赖于实验模型的可用性,允许在实验室环境中进行调查。在这里,我们详细介绍了三种基于细胞的滤泡性甲状腺癌模型的发展和特征,这些模型非常接近地模拟了患者中所见疾病的遗传和病理进展,包括在某些情况下进展为低分化和间变性甲状腺癌。我们预计,这些新开发的模型将允许发现疾病进展的新机制和治疗干预的测试。由于缺乏有效的体外模型,使得临床前实验和前瞻性治疗方法的筛选无法进行,甲状腺癌研究的最新进展受到阻碍。这项工作的目的是开发和表征三种新型滤泡性甲状腺癌(FTC)细胞系,这些细胞系是从相关动物模型中发展而来的。这些细胞系概括了FTC的遗传和组织病理学特征,以及向低分化状态的进展。我们证明,这些细胞系可以用于各种体外应用,并保持在体内移植到免疫能力强的宿主的潜力。此外,细胞系表现出不同程度的生长失调和侵袭性行为,这可能有助于确定患者群体中存在异质性的发病机制。我们相信这些新的细胞系将为研究甲状腺癌进展的分子基础提供有力的工具,并导致更个性化的诊断和治疗策略的发展。
Advancements in thyroid cancer are dependent on the availability of experimental models allowing for investigation in the laboratory setting. Here, we detail the development and characterization of three cell-based models of follicular thyroid cancer that closely mimic the genetic and pathological progression of the disease seen in patients, including progression to poorly differentiated and anaplastic thyroid cancer in some cases. We anticipate that these newly developed models will allow for the discovery of novel mechanisms of disease progression and the testing of therapeutic interventions. Recent developments in thyroid cancer research have been hindered by a lack of validated in vitro models, allowing for preclinical experimentation and the screening of prospective therapeutics. The goal of this work is to develop and characterize three novel follicular thyroid cancer (FTC) cell lines developed from relevant animal models. These cell lines recapitulate the genetics and histopathological features of FTC, as well as progression to a poorly differentiated state. We demonstrate that these cell lines can be used for a variety of in vitro applications and maintain the potential for in vivo transplantation into immunocompetent hosts. Further, cell lines exhibit differing degrees of dysregulated growth and invasive behavior that may help define mechanisms of pathogenesis underlying the heterogeneity present in the patient population. We believe these novel cell lines will provide powerful tools for investigating the molecular basis of thyroid cancer progression and lead to the development of more personalized diagnostic and treatment strategies.
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