Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Mol Cancer Res. 2019 May;17(5):1036-1048. doi: 10.1158/1541-7786.MCR-18-1026. Epub 2019 Feb 7.
Cancer cell lines are critical models to study tumor progression and response to therapy. In 2008, we showed that approximately 50% of thyroid cancer cell lines were redundant or not of thyroid cancer origin. We therefore generated new authenticated thyroid cancer cell lines and patient-derived xenograft (PDX) models using and feeder cell approaches, and characterized these models and . We developed four thyroid cancer cell lines, two derived from 2 different patients with papillary thyroid cancer (PTC) pleural effusions, CUTC5, and CUTC48; one derived from a patient with anaplastic thyroid cancer (ATC), CUTC60; and one derived from a patient with follicular thyroid cancer (FTC), CUTC61. One PDX model (CUTC60-PDX) was also developed. Short tandem repeat (STR) genotyping showed that each cell line and PDX is unique and match the original patient tissue. The CUTC5 and CUTC60 cells harbor the BRAF (V600E) mutation, the CUTC48 cell line expresses the RET/PTC1 rearrangement, and the CUTC61 cells have the HRAS (Q61R) mutation. Moderate to high levels of and variable levels of were detected in each cell line and PDX. The CUTC5 and CUTC60 cell lines form tumors in orthotopic and flank xenograft mouse models. IMPLICATIONS: We have developed the second RET/PTC1-expressing PTC-derived cell line in existence, which is a major advance in studying RET signaling. We have further linked all cell lines to the originating patients, providing a set of novel, authenticated thyroid cancer cell lines and PDX models to study advanced thyroid cancer.
癌细胞系是研究肿瘤进展和对治疗反应的重要模型。2008 年，我们表明大约 50%的甲状腺癌细胞系是冗余的或不是甲状腺癌起源的。因此，我们使用 和饲养细胞方法生成了新的经过验证的甲状腺癌细胞系和患者来源的异种移植（PDX）模型，并对这些模型进行了 和 。我们开发了 4 种甲状腺癌细胞系，其中 2 种源自 2 名患有甲状腺乳头状癌（PTC）胸腔积液的不同患者，即 CUTC5 和 CUTC48；1 种源自患有间变性甲状腺癌（ATC）的患者，即 CUTC60；1 种源自患有滤泡性甲状腺癌（FTC）的患者，即 CUTC61。还开发了 1 个 PDX 模型（CUTC60-PDX）。短串联重复（STR）基因分型表明，每个细胞系和 PDX 都是独特的，并与原始患者组织相匹配。CUTC5 和 CUTC60 细胞携带 BRAF（V600E）突变，CUTC48 细胞系表达 RET/PTC1 重排，CUTC61 细胞具有 HRAS（Q61R）突变。在每个细胞系和 PDX 中均检测到中等至高水平的 和可变水平的 。CUTC5 和 CUTC60 细胞系在原位和侧翼异种移植小鼠模型中形成肿瘤。意义：我们已经开发了第二个存在的 RET/PTC1 表达的 PTC 衍生细胞系，这是研究 RET 信号的重大进展。我们进一步将所有细胞系与起源患者联系起来，提供了一组新的、经过验证的甲状腺癌细胞系和 PDX 模型，用于研究晚期甲状腺癌。
