Identification and chemoresistance of cancer stem cells in HPV-negative oropharyngeal cancer

HPV 阴性口咽癌中癌症干细胞的鉴定及化学耐药性

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作者:Mehmet Gunduz, Esra Gunduz, Shunji Tamagawa, Keisuke Enomoto, Muneki Hotomi

Abstract

The underlying mechanisms of resistance to chemoradiotherapy of human papilloma virus (HPV)-negative patients with oropharyngeal cancer (OPC) remain unclear. The present study aimed to characterize cancer stem cells (CSC) of the HPV-negative OPC cell line in terms of chemotherapy resistance. CSCs were isolated through magnetic activated cell sorting using the CSC specific marker aldehyde dehydrogenase 1 antibody, and characterized by sphere formation capacity, immunofluorescence staining, and CSC marker expression. CSC response to cisplatin treatment was evaluated via XTT-assays. Spheres of CSCs of the HPV-negative UTSCC-60A cell line were highly dark holospheres. RNA expression levels of CSC markers OCT4, SOX2, Kruppel-like factor 4 and BMI1 were significantly higher in CSC. CSCs were significantly resistant to cisplatin treatment at various dosages compared with nonCSC. The present study suggested that the proportion of CSCs is very low in the tumor bulk, CSCs are resistant to cisplatin in HPV-negative OPC, which requires further investigation to define their mechanism.

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