在脂肪细胞和癌细胞之间的界面上的补充激活驱动瘤进展
Andres Valdivia1, Ana Maria Isac1, Horacio Cardenas1
1Department of Obstetrics and Gynecology.
JCI insight
|February 18, 2025
概括
体中的脂肪细胞通过将脂质转移到癌细胞中来促进卵巢癌 (OC) 转移. 这激活了综合应激反应 (ISR),增加了补充C3 / C5蛋白,并推动了瘤的生长.
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 癌症转移 癌症转移
背景情况:
- 预兆是卵巢癌 (OC) 转移的频繁地点.
- 脂肪细胞与癌细胞的相互作用在OC中促进了侵袭性和转移性表型.
研究的目的:
- 研究OC转移中的癌细胞-脂肪细胞交叉的分子机制.
- 确定参与脂肪细胞驱动的OC进展的关键途径和分子.
主要方法:
- 用OC细胞直接培养永久化的人体内脏非糖尿病前脂质细胞 (VNPADs).
- RNA测序用于分析共同培养的OC细胞中的转录基因变化.
- 在体外功能测定和体内瘤进展模型.
- 对补充C3和C5蛋白的表达和功能的分析.
主要成果:
- 与单一培养细胞相比,共同培养的OC细胞表现出增加的增殖,侵入性和对西斯普拉丁的抗性.
- 观察到显著的转录基因变化,其中包括PI3K/AKT和补充激活等丰富的途径.
- 从脂肪细胞转移的脂质诱导了OC细胞中补充C3和C5蛋白的上调.
- 抑制C3/C5逆转了侵袭性,而C3敲击降低了体内瘤进展.
- 在高BMI患者的OMental植入物和OC瘤中发现了增加的C3表达.
- C3上调涉及到ATF4介导的综合应激反应 (ISR).
结论:
- 脂肪细胞与癌细胞的相互作用促进了OC的侵入性和瘤发生.
- 脂质转移,ISR激活和补充C3 / C5上调是关键机制.
- 针对这些途径可能为OC转移提供治疗策略.
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