Institute of Genetic Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle Upon-Tyne NE1 3BZ, UK.
Institute of Genetic Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle Upon-Tyne NE1 3BZ, UK; Department of Surgery, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia.
Exp Cell Res. 2019 Jan 1;374(1):104-113. doi: 10.1016/j.yexcr.2018.11.012. Epub 2018 Nov 19.
Comparison of studies of cells derived from normal and pathological tissues of the same organ can be fraught with difficulties, particular with cancer where a number of different diseases are considered cancer within the same tissue. In the thyroid, there are 4 main types of cancer, three of which arise from follicular epithelial cells; papillary and follicular which are classified as differentiated, and anaplastic which is classified as undifferentiated. One assay that can be utilised for isolation of cancer stem cells is the side population (SP) assay. However, SP studies have been limited in part due to lack of optimal isolation strategies and in the case of anaplastic thyroid cancer (ATC) are further compounded by lack of access to ATC tumors. We have used thyroid cell lines to determine the optimal conditions to isolate viable SP cells. We then compared SP cells and NSP cells (bulk tumour cells without the SP) of a normal thyroid cell line N-thy ori-3-1 and an anaplastic thyroid cancer cell line SW1736 and showed that both SP cell populations displayed higher levels of stem cell characteristics than the NSP. When we compared SP cells of the N-thy ori-3-1 and the SW1736, the SW1736 SP had a higher colony forming potential, expressed higher levels of stem cell markers and CXCR4 and where more migratory and invasive, invasiveness increasing in response to CXCL12. This is the first report showing functional differences between ATC SP and normal thyroid SP and could lead to the identification of new therapeutic targets to treat ATC.
比较同一器官的正常组织和病变组织来源的细胞的研究可能充满困难，尤其是在癌症中，同一组织中的许多不同疾病都被认为是癌症。在甲状腺中，有 4 种主要的癌症类型，其中 3 种起源于滤泡上皮细胞；乳头状和滤泡状被归类为分化型，间变性被归类为未分化型。一种可用于分离癌症干细胞的检测方法是侧群（SP）检测。然而，SP 研究受到限制，部分原因是缺乏最佳的分离策略，而对于间变性甲状腺癌（ATC），由于无法获得 ATC 肿瘤，情况进一步恶化。我们使用甲状腺细胞系来确定分离活 SP 细胞的最佳条件。然后，我们比较了正常甲状腺细胞系 N-thy ori-3-1 和间变性甲状腺癌细胞系 SW1736 的 SP 细胞和 NSP 细胞（没有 SP 的大量肿瘤细胞），结果表明两种 SP 细胞群都显示出更高水平的干细胞特征，比 NSP 细胞高。当我们比较 N-thy ori-3-1 和 SW1736 的 SP 细胞时，SW1736 的 SP 具有更高的集落形成能力，表达更高水平的干细胞标志物和 CXCR4，并且更具迁移和侵袭性，对 CXCL12 的反应性增加。这是首次报道 ATC SP 和正常甲状腺 SP 之间存在功能差异的报告，这可能会导致确定新的治疗 ATC 的治疗靶点。
