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无塑性甲状腺癌细胞降低CD71水平以增加铁过载耐受性
Simona D'Aprile1, Simona Denaro1, Anna Maria Pavone1
1Department of Biomedical and Biotechnological Sciences, University of Catania, 95123, Catania, Italy.
Journal of translational medicine
|November 4, 2023
概括
毛囊性甲状腺癌细胞在铁过载下显示出增加的铁亡,不同于通过调节CD71.1而抵抗其的无塑性甲状腺癌细胞. 这种差异性的铁灭症耐受性对治疗侵袭性厌塑性甲状腺癌有影响.
科学领域:
- 在瘤学瘤学.
- 细胞死亡机制 细胞死亡机制
- 癌症治疗方法 癌症治疗方法
背景情况:
- 毛囊性甲状腺癌 (FTC) 是常见的,而厌塑性甲状腺癌 (ATC) 是罕见的,具有攻击性和具有挑战性的治疗.
- 铁,一种依赖于铁的细胞死亡,是一种潜在的癌症疗法,但有些癌症抵抗其作用.
- 了解差异性ferroptosis敏感性对于开发有效的癌症治疗是至关重要的.
研究的目的:
- 研究依赖铁的细胞死亡 (ferroptosis) 对不同类型的甲状腺癌的影响.
- 分析甲状腺癌中铁灭症抵抗的基础分子机制.
- 探索铁灭症耐受性在甲状腺癌治疗中的临床影响.
主要方法:
- 使用FTC和ATC细胞系 (FTC-133和8505C) 的人体活检和体外模型.
- 通过使用MTT测定,克隆基因测定和流细胞计,评估细胞活力,增殖和铁.
- 通过脂质过氧化试验和西部涂抹分析了铁酶调节的分子机制,模拟铁酸的铁过载.
主要成果:
- 在铁过载时,FTC-133细胞的活力降低,铁亡增加.
- 8505C细胞表现出对铁亡的更强耐受性,调节CD71以保持生命力.
- CD71在形甲状腺癌中对铁的内化和铁的抗性起作用.
结论:
- 甲状腺癌细胞表现出对铁亡的差异性耐受性,FTC比ATC更敏感.
- ATC对铁灭的抵抗,可能由CD71调解,这对治疗提出了挑战.
- 向铁亡途径可能为治疗侵袭性形甲状腺癌提供新的策略.
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