巨细胞酶控制了胰腺癌中代谢压力驱动的CAF亚型身份
Yijuan Zhang1, Li Ling1, Swetha Maganti1
1Cancer Metabolism and Microenvironment Program, NCI-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
bioRxiv : the preprint server for biology
|December 16, 2024
概括
胰腺癌细胞和CAF通过增加宏皮诺细胞分裂来适应低谷氨. 阻止这个过程会改变与癌症相关的纤维细胞亚型和瘤层,使胰腺癌对治疗敏感.
科学领域:
- 在瘤学瘤学.
- 癌症生物学 癌症生物学
- 瘤微环境 瘤微环境
背景情况:
- 胰腺管道腺癌 (PDAC) 表现出谷氨酸缺乏,影响瘤细胞和癌症相关纤维细胞 (CAF).
- 无论是PDAC细胞还是CAF细胞,都利用宏皮诺细胞酶作为对谷氨酸缺乏的适应性反应.
- 代谢应激适应在塑造CAF身份和瘤肌层的作用仍然不清楚.
研究的目的:
- 研究代谢性压力如何影响CAF亚型和PDAC中的瘤肌层.
- 确定宏皮诺细胞体在限制谷氨胺下调节CAF身份中的作用.
- 探索针对PDAC中的代谢适应的治疗策略.
主要方法:
- 使用PDAC的体内模型.
- 研究了阻断巨细胞细胞形成对CAF亚型和 stromal 结构的影响.
- 分析了参与CAF编程的MEK/ERK信号通路.
主要成果:
- 代谢压力会诱导一种由MEK/ERK信号介导的内在炎症CAF (iCAF) 程序.
- 抑制巨细胞细胞分裂会改变CAF亚型,并重组瘤层.
- 通过巨细胞结合阻断调节树皮结构,使PDAC对免疫疗法和化疗敏感.
结论:
- 代谢压力是PDAC中瘤微环境重塑的关键驱动因素.
- 在代谢压力下,巨型皮细胞体调节CAF的身份和 stromal组织.
- 向巨细胞和其下游影响为胰腺癌提供了一个有前途的治疗策略.
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