Lee-Theilen Mieun, Fadini Delaine D, Hadhoud Julia R, van Dongen Fleur, Kroll Gabriela, Rolle Udo, Fiegel Henning C
Department of Pediatric Surgery and Pediatric Urology, University Hospital, Goethe University Frankfurt, 60590 Frankfurt, Germany.
Cancers (Basel). 2022 Nov 25;14(23):5825. doi: 10.3390/cancers14235825.
The biology of cancer stem cells (CSCs) of pediatric cancers, such as hepatoblastoma, is sparsely explored. This is mainly due to the very immature nature of these tumors, which complicates the distinction of CSCs from the other tumor cells. Previously, we identified a CSC population in hepatoblastoma cell lines expressing the CSC markers CD34 and CD90, cell surface Vimentin (csVimentin) and binding of OV-6. In this study, we detected the co-expression of the immune escape factor PD-L1 in the CSC population, whereas the other tumor cells remained negative. FACS data revealed that non-CSCs give rise to CSCs, reflecting plasticity of CSCs and non-CSCs in hepatoblastoma as seen in other tumors. When we treated cells with cisplatin and decitabine, a new CD34OV-6CD90 population emerged that lacked csVimentin and PD-L1 expression. Expression analyses showed that this new CSC subset shared similar pluripotency and EMT features with the already-known CSCs. FACS results further revealed that this subset is also generated from non-CSCs. In conclusion, we showed that hepatoblastoma CSCs express PD-L1 and that the biology of hepatoblastoma CSCs is of a plastic nature. Chemotherapeutic treatment leads to another CSC subset, which is highly chemoresistant and could be responsible for a poor prognosis after postoperative chemotherapy.
小儿癌症（如肝母细胞瘤）的癌症干细胞（CSCs）生物学研究较少。这主要是由于这些肿瘤非常不成熟，使得区分CSCs与其他肿瘤细胞变得复杂。此前，我们在肝母细胞瘤细胞系中鉴定出一个表达CSC标志物CD34和CD90、细胞表面波形蛋白（csVimentin）以及与OV-6结合的CSC群体。在本研究中，我们检测到免疫逃逸因子PD-L1在CSC群体中共同表达，而其他肿瘤细胞仍为阴性。流式细胞术数据显示，非CSCs可产生CSCs，这反映了肝母细胞瘤中CSCs和非CSCs的可塑性，这在其他肿瘤中也有发现。当我们用顺铂和地西他滨处理细胞时，出现了一个新的CD34OV-6CD90群体，该群体缺乏csVimentin和PD-L1表达。表达分析表明，这个新的CSC亚群与已知的CSCs具有相似的多能性和上皮-间质转化特征。流式细胞术结果进一步显示，这个亚群也由非CSCs产生。总之，我们表明肝母细胞瘤CSCs表达PD-L1，且肝母细胞瘤CSCs的生物学特性具有可塑性。化疗导致另一个CSC亚群的出现，该亚群具有高度化疗抗性，可能是术后化疗预后不良的原因。
