对于作为新的癌症治疗靶点的肿瘤干细胞（CSCs）激活的膜转运体的潜力越来越受到关注。因此，本研究调查了食管腺癌（EAC）中CSCs的离子转运相关分子表达谱。通过荧光活化细胞分选术，将高度表达醛脱氢酶1家族成员A1（ALDH1A1）的细胞从人巴雷特食管腺癌细胞系OE33中分离出来。根据肿瘤球形体的形成来鉴定CSCs。通过微阵列分析检测了CSCs的基因表达谱。OE33细胞中，CSCs中ALDH1A1信使RNA水平高于非CSCs。此外，CSCs对顺铂具有抗性，并且具有再分化的能力。CSCs的微阵列分析结果显示了与离子通道/转运体有关的多个基因的上调表达，例如瞬时受体电位热敏通道2（TRPV2）和溶质载体家族12成员2（SLC12A2）。TRPV2抑制剂曲尼拉斯和SLC12A2抑制剂呋塞米在CSCs中浓度较低时的细胞毒性较高，两者均显著减少了肿瘤球数量。高度表达ALDH1A1的OE33细胞亚群也显著减少了这些抑制剂。根据目前的结果，TRPV2和SLC12A2参与CSCs的维持，并且它们的特异性抑制剂曲尼拉斯和呋塞米分别具有作为EAC的靶向治疗剂的潜力。© 2023年。外科肿瘤学会。

The potential of membrane transporters activated in cancer stem cells (CSCs) as new therapeutic targets for cancer is attracting increasing interest. Therefore, the present study examined the expression profiles of ion transport-related molecules in the CSCs of esophageal adenocarcinoma (EAC).Cells that highly expressed aldehyde dehydrogenase 1 family member A1 (ALDH1A1) were separated from OE33 cells, a human Barrett's EAC cell line, by fluorescence-activated cell sorting. CSCs were identified based on the formation of tumorspheres. Gene expression profiles in CSCs were examined by a microarray analysis.Among OE33 cells, ALDH1A1 messenger RNA levels were higher in CSCs than in non-CSCs. Furthermore, CSCs exhibited resistance to cisplatin and had the capacity to redifferentiate. The results of the microarray analysis of CSCs showed the up-regulated expression of several genes related to ion channels/transporters, such as transient receptor potential vanilloid 2 (TRPV2) and solute carrier family 12 member 2 (SLC12A2). The cytotoxicities of the TRPV2 inhibitor tranilast and the SLC12A2 inhibitor furosemide were higher at lower concentrations in CSCs than in non-CSCs, and both markedly reduced the number of tumorspheres. The cell population among OE33 cells that highly expressed ALDH1A1 also was significantly decreased by these inhibitors.Based on the present results, TRPV2 and SLC12A2 are involved in the maintenance of CSCs, and their specific inhibitors, tranilast and furosemide, respectively, have potential as targeted therapeutic agents for EAC.© 2023. Society of Surgical Oncology.