Overcoming the lack of expression of the sodium-iodide symporter protein in anaplastic thyroid cancer stem cells by targeting the phosphatidyl inositol 3-kinase signaling pathway

Background: Anaplastic thyroid carcinoma (ATC) is rare, but it is the most aggressive thyroid cancer. Cancer stem cells (CSCs), which have self-renewal ability and can generate multi-lineage cells, are potential causative agents for ATC recurrence. To assess the role of CSCs in ATC, we evaluated the sodium-iodide symporter (NIS or SLC5A5) and Phosphatidyl Inositol 3-Kinase (PI3K) mRNA levels in the (CD133pos) CSC fraction of ATC cell lines. Methods: Using magnetic cell sorting, we isolated (CD133pos) CSCs from three ATC cell lines. After verification of the cell purity by flow cytometry, the NIS and PI3K mRNA levels were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). We performed immunocytochemistry to determine NIS protein localization after treated these cells with LY294002, a PI3K inhibitor. Results: The qRT-PCR results revealed that the (CD133pos) CSCs extracted from the ATC cell lines had lower NIS mRNA expression and higher PI3K mRNA expression than normal human thyrocytes. In addition, the cells were capable of expressing the NIS protein, but only after PI3K inhibitor treatment. Conclusion: High PI3K levels in (CD133pos) CSCs may impair NIS gene and protein expression. The lack of NIS gene and protein expression in these cells may be a critical reason for radioiodine therapy resistance in patients with ATC. Targeting the CSCs along with conventional thyroid cancer therapy may be a useful molecular curative approach for treating aggressive carcinomas, especially ATC, in the future.