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The effects of hyperthermia on human hepatocellular carcinoma stem and mature cancer cells. INTRODUCTION AND OBJECTIVES: Hepatocellular carcinoma (HCC) can recur following radiofrequency ablation and other hyperthermic treatment modalities. Cancer stem cells (CSCs) are a subpopulation of HCC cells that are difficult to eradicate and largely responsible for tumor recurrences. Thus, the principal objective of this study was to determine whether human HCC CSCs are relatively thermal-resistant compared to non-stem or mature cancer cells (MCCs). MATERIALS AND METHODS: Epithelial cell adhesion molecule (EpCAM) positive enriched CSCs and EpCAM- MCCs were derived from a human HCC cell line using fluorescence activated cell sorting. Each cell population was exposed to 65°C heat for 0-16min and survival documented at various time points. RESULTS: Cell survival curves were similar in CSC and MCCs throughout the 16min heat exposure period. Maximum killing was obtained after 12-14min of heat exposure. Cytoprotective, heat shock proteins-70 (HSP70) and -90 (HSP90) mRNA expression were not disproportionately increased in CSCs. CONCLUSIONS: These results suggest that human HCC CSCs are not more thermal resistant than MCCs and therefore, do not support the hypothesis that HCC recurrences following hyperthermic treatment reflect CSC thermal-resistance.