Nanog is a promising chemoresistant stemness marker and therapeutic target by iron chelators for esophageal cancer
Nanog is a promising chemoresistant stemness marker and therapeutic target by iron chelators for esophageal cancer
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DOI：
10.1002/ijc.33544
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发表时间：
2021-04-05
影响因子：
6.4
通讯作者：
Fujiwara, Toshiyoshi
中科院分区：
文献类型：
--
作者：
Narusaka, Toru;Ohara, Toshiaki;Fujiwara, Toshiyoshi
食管癌是一种预后不良的疾病。尽管使用顺铂 (CDDP) 和 5-氟尿嘧啶的联合化疗是不可切除食管癌的标准化疗，但缓解率为 35%。据报道，癌症干细胞（CSC）和炎症是导致食管癌预后不良的原因。然而，尚未进行全面分析，也缺乏取得进展的建议。众所周知，铁是 CSC 干性的关键因素。我们的研究重点是使用铁螯合剂控制食管癌 CSC 的铁治疗潜力。在134例免疫组化分析的病例中，Nanog表达高的有98例，低表达的有36例。 Nanog 高表达与低总体生存率和无病生存率相关。铁螯合剂地拉罗司 (DFX) 和 SP10 抑制 TE8 和 OE33 细胞中的增殖和干细胞标记物的表达。 DFX 和 SP10 不诱导代偿性白细胞介素 (IL)-6 分泌，尽管 CDDP 确实导致高诱导。此外，BBI608和SSZ与其他CSC靶向药物一样，不能抑制干性标志物的表达。总体而言，Nanog 表达似乎与食管癌患者的不良预后相关，铁螯合剂抑制干性和代偿性 IL-6 分泌可能为食管癌提供一种新的治疗策略。
Esophageal cancer is a disease showing poor prognosis. Although combination chemotherapy using cisplatin (CDDP) and 5-fluorouracil is standard for unresectable esophageal cancer, the response rate is 35%. Cancer stem cells (CSCs) and inflammation are reportedly responsible for the poor prognosis of esophageal cancer. However, comprehensive analyses have not been conducted and proposals for progress remain lacking. Iron is known to be a key factor in the stemness of CSCs. Our study focused on the therapeutic potential of iron control using iron chelators for CSCs in esophageal cancer. Among 134 immunohistochemically analyzed cases, Nanog expression was high in 98 cases and low in 36 cases. High Nanog expression correlated with low overall and disease-free survivals. The iron chelators deferasirox (DFX) and SP10 suppressed the proliferation and expression of stemness markers in TE8 and OE33 cells. DFX and SP10 did not induce compensatory interleukin (IL)-6 secretion, although CDDP did result in high induction. Moreover, BBI608 and SSZ, as other CSC-targeting drugs, could not suppress the expression of stemness markers. Overall, Nanog expression appears related to poor prognosis in esophageal cancer patients, and inhibition of stemness and compensatory IL-6 secretion by iron chelators may offer a novel therapeutic strategy for esophageal cancer.