在多发性骨髓瘤中解锁药物耐药性:脂肪细胞作为治疗反应调节器
Maria Ochiai1, Sara Fierstein1, Farouq XsSali1
1Department of Biology, American University, 4400 Massachusetts Ave, NW, Washington, DC 20016, USA.
Cancers
|September 9, 2023
概括
肥胖症通过促进耐药性,使多发性骨髓瘤 (MM) 治疗结果恶化. 超重和肥胖个体的脂肪细胞增强了MM细胞的存活率和耐药性,使它们能够抵抗诸如博尔特佐米布之类的疗法.
科学领域:
- 血液学 血液学 血液学
- 在瘤学瘤学.
- 代谢综合征是代谢综合征的一种.
背景情况:
- 多发性骨髓瘤 (MM) 是一种无法治愈的血液癌症,具有越来越强的抗药性.
- 肥胖是MM的风险因素,但其在治疗耐药性方面的作用尚不清楚.
研究的目的:
- 调查脂肪细胞-MM细胞相互作用是否促进药物耐药性.
- 为了确定肥胖是否会放大这种效应.
主要方法:
- 脂肪细胞与正常,超重和肥胖的捐赠者的人类脂肪衍生干细胞 (ASC) 不同.
- 脂肪细胞与MM细胞系的共同培养 (RPMI 8226,U266B1).
- 用MM疗法进行治疗 (博尔特佐米布或博尔特佐米布/德克萨米萨/莱纳利多米德).
主要成果:
- 超重/肥胖个体的脂肪细胞增加了MM细胞的细胞粘附介导药物耐药性 (CAM-DR).
- 药物载体P-糖蛋白 (P-gp) 和MRP的增强表达.
- 增加了体外血管生成和MMP-2活性.
- 保护MM细胞免受药物诱导的死亡.
结论:
- 与肥胖相关的脂肪细胞通过CAM-DR和改变的输送体表达,促进MM药物耐药性.
- 这种交叉通话机制可能解释了肥胖如何促进MM的进展和复发.
- 准脂肪细胞-MM细胞相互作用可能是一个治疗策略.
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