Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Thyroid. 2011 Sep;21(9):1001-7. doi: 10.1089/thy.2011.0030. Epub 2011 Jul 18.
Poorly differentiated and anaplastic thyroid carcinomas have a rather poor prognosis. The development of relevant model systems to unravel in vitro and in vivo the molecular mechanisms governing the resistance of these tumors to therapy, as well as to test novel drug combinations, is a clear priority for thyroid-focused research.
Several novel cell lines were established from tumors developed by mice engineered to simultaneously express a loss-of-function Pten allele and an oncogenic Kras allele.
Similar to most poorly differentiated thyroid tumors, these cell lines are characterized by simultaneous activation of the PI3K and MAPK pathways, by the presence of wild-type, functional p53, and by the severe downregulation of thyroid differentiation markers, including sodium-iodide symporter (NIS). Further, they display a highly glycolytic phenotype. They can be grafted to syngeneic, immunocompetent hosts, and easily metastasize to the lungs.
These mouse cell lines are a novel and invaluable tool that can be used to develop innovative therapeutic approaches to poorly differentiated carcinomas in a more physiological context than using xenografts of human cell lines in immunocompromised mice.
低分化和间变性甲状腺癌的预后较差。开发相关的模型系统，以揭示控制这些肿瘤对治疗产生抗性的体内和体外分子机制，并测试新的药物组合，这是甲状腺研究的当务之急。
从同时表达功能丧失的 Pten 等位基因和致癌性 Kras 等位基因的工程小鼠中发展而来的几种新型细胞系。
与大多数低分化甲状腺肿瘤相似，这些细胞系的特征是同时激活 PI3K 和 MAPK 途径，存在野生型、功能性 p53，并严重下调甲状腺分化标志物，包括钠碘转运体（NIS）。此外，它们还表现出高度的糖酵解表型。它们可以被移植到同种异体、免疫功能正常的宿主中，并容易转移到肺部。
这些小鼠细胞系是一种新颖且非常宝贵的工具，可用于在比使用免疫缺陷小鼠中异种移植人细胞系更具生理相关性的情况下，开发针对低分化癌的创新治疗方法。
