骨髓脂肪细胞通过隔离多克索鲁比来促进瘤微环境驱动的化学抵抗
Jun-Goo Kwak1, Jungwoo Lee1,2,3
1Molecular and Cellular Biology Graduate Program, University of Massachusetts Amherst, Amherst, MA 01003, USA.
Cancers
|June 22, 2023
概括
骨髓中的成熟脂肪细胞可以通过将化疗药物分离到脂质滴中来引起化学抵抗. 这一发现揭示了一个新的机制,导致骨转移的治疗失败.
科学领域:
- 生物医学工程 生物医学工程
- 癌症生物学 癌症生物学
- 细胞生物学 细胞生物学
背景情况:
- 化学抵抗是治疗骨转移的一个主要障碍.
- 骨髓脂肪细胞是关键的 stromal 细胞,可能会影响化学抵抗.
- 由于解剖学和组织的复杂性,研究骨髓微环境是具有挑战性的.
研究的目的:
- 开发骨髓脂肪细胞的体外模型.
- 为了研究脂肪细胞诱导的化学抵抗机制.
- 探索脂肪细胞在骨转移治疗耐药性的作用.
主要方法:
- 通过使用罗西格利塔分化人类骨髓 stromal 细胞 (hBMSCs) 变成脂肪细胞.
- 在水凝支架中创建3D脂肪细胞球形,模仿骨髓侧面形状.
- 在 doxorubicin 治疗下与 3D 脂肪细胞共同培养多发性骨髓瘤细胞.
主要成果:
- 成熟的脂肪细胞在脂质滴中隔离多克索鲁比辛,降低其细胞毒性.
- 在3D脂肪细胞模型中对多发性骨髓瘤细胞的 doxorubicin 治疗加速了癌细胞的增殖.
- 化学疗法药物的脂肪细胞封存被确定为一种化学抵抗机制.
结论:
- 成熟的脂肪细胞有助于骨髓微环境驱动的化学抵抗.
- 脂肪细胞对疏水性化疗药物的隔离是一个重要的机制.
- 试验室模型提供了关于骨转移中脂肪细胞介导的化学抵抗的见解.
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