在老化的膀中,先前存在的衰老性纤维细胞通过CXCL12分泌产生瘤宽容的利基
Satoru Meguro1,2, Yoshikazu Johmura3,4, Teh-Wei Wang1
1Division of Cancer Cell Biology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Nature aging
|September 9, 2024
概括
衰老通过增加分泌CXCL12的衰老纤维细胞促进膀癌. 消除这些细胞或阻断CXCL12信号显著抑制了小鼠模型中的瘤生长.
科学领域:
- 在瘤学瘤学.
- 老年学是指老年学的学科.
- 细胞生物学 细胞生物学
背景情况:
- 衰老是癌症发展的重要危险因素.
- 将衰老与癌症风险增加联系在一起的机制尚未完全理解.
- 细胞衰老,以p16蛋白为特征,与衰老有关.
研究的目的:
- 调查与衰老相关的衰老纤维细胞在促进膀癌中的作用.
- 确定衰老细胞对致癌产生有助的分子机制.
- 探索针对膀癌老化的细胞的治疗策略.
主要方法:
- 利用了经过基因改造的小鼠膀癌模型.
- 采用单细胞RNA测序来分析老年小鼠的纤维细胞基因表达.
- 在体内研究了消除p16高衰老细胞和抑制CXCL12信号传递对瘤生长的影响.
主要成果:
- 在老鼠膀中,p16高衰老纤维细胞 (p16h-sn) 随着年龄的增长而积累.
- p16h-sn纤维细胞作为炎症性癌症相关纤维细胞 (CAF) 起作用,促进瘤生长.
- 单细胞RNA测序在p16h-sn纤维细胞中发现了更高的CXCL12表达.
- 消除p16h-sn细胞或抑制CXCL12抑制了膀瘤的生长.
- 鉴定了一种p16h-sn CAFs的基因特征 (SMOC2,GUCY1A1,CXCL12,CRISPLD2,GAS1,LUM),与人类膀癌患者的预后不佳有关.
结论:
- 在老化的膀中,高衰老的纤维细胞形成了一个亲瘤的微环境.
- 这些衰老的纤维细胞主要通过CXCL12分泌促进膀瘤的生长.
- 针对衰老细胞和CXCL12信号传递,代表了与年龄相关的膀癌的潜在治疗策略.
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