Institute of Clinical Medicine, National Yang Ming University, Taipei, Taiwan.
Eur J Nucl Med Mol Imaging. 2013 Jan;40(1):61-71. doi: 10.1007/s00259-012-2242-5. Epub 2012 Oct 19.
(131)I therapy is regularly used following surgery as a part of thyroid cancer management. Despite an overall relatively good prognosis, recurrent or metastatic thyroid cancer is not rare. CD133-expressing cells have been shown to mark thyroid cancer stem cells that possess the characteristics of stem cells and have the ability to initiate tumours. However, no studies have addressed the influence of CD133-expressing cells on radioiodide therapy of the thyroid cancer. The aim of this study was to investigate whether CD133(+) cells contribute to the radioresistance of thyroid cancer and thus potentiate future recurrence and metastasis.
Thyroid cancer cell lines were analysed for CD133 expression, radiosensitivity and gene expression.
The anaplastic thyroid cancer cell line ARO showed a higher percentage of CD133(+) cells and higher radioresistance. After γ-irradiation of the cells, the CD133(+) population was enriched due to the higher apoptotic rate of CD133(-) cells. In vivo (131)I treatment of ARO tumour resulted in an elevated expression of CD133, Oct4, Nanog, Lin28 and Glut1 genes. After isolation, CD133(+) cells exhibited higher radioresistance and higher expression of Oct4, Nanog, Sox2, Lin28 and Glut1 in the cell line or primarily cultured papillary thyroid cancer cells, and lower expression of various thyroid-specific genes, namely NIS, Tg, TPO, TSHR, TTF1 and Pax8.
This study demonstrates the existence of CD133-expressing thyroid cancer cells which show a higher radioresistance and are in an undifferentiated status. These cells possess a greater potential to survive radiotherapy and may contribute to the recurrence of thyroid cancer. A future therapeutic approach for radioresistant thyroid cancer may focus on the selective eradication of CD133(+) cells.
(131)I 治疗通常作为甲状腺癌管理的一部分,在手术后使用。尽管总体预后相对较好,但甲状腺癌的复发或转移并不罕见。已经表明,表达 CD133 的细胞标记甲状腺癌干细胞,这些细胞具有干细胞的特征,并具有引发肿瘤的能力。然而,尚无研究探讨表达 CD133 的细胞对甲状腺癌细胞碘放射性治疗的影响。本研究旨在探讨 CD133(+)细胞是否有助于甲状腺癌细胞的放射抵抗,从而增强未来的复发和转移。
分析甲状腺癌细胞系的 CD133 表达、放射敏感性和基因表达。
间变性甲状腺癌细胞系 ARO 表现出更高比例的 CD133(+)细胞和更高的放射抵抗性。γ 射线照射细胞后,由于 CD133(-)细胞的凋亡率更高,CD133(+)细胞群体得到富集。在 ARO 肿瘤的体内(131)I 治疗中,CD133、Oct4、Nanog、Lin28 和 Glut1 基因的表达升高。分离后,CD133(+)细胞在细胞系或原代培养的甲状腺乳头状癌细胞中表现出更高的放射抵抗性和更高的 Oct4、Nanog、Sox2、Lin28 和 Glut1 表达,以及各种甲状腺特异性基因的表达降低,即 NIS、Tg、TPO、TSHR、TTF1 和 Pax8。
本研究表明存在表达 CD133 的甲状腺癌细胞,这些细胞表现出更高的放射抵抗性,处于未分化状态。这些细胞具有更大的生存放射治疗的潜力,可能有助于甲状腺癌的复发。针对放射性抵抗性甲状腺癌的未来治疗方法可能集中在选择性清除 CD133(+)细胞上。