治疗引起的正常组织损伤促进了乳腺癌的转移
Douglas W Perkins1, Ivana Steiner1, Syed Haider1
1The Breast Cancer Now Toby Robins Research Centre, Institute of Cancer Research, 237 Fulham Road, SW3 6JB London, UK.
iScience
|January 1, 2024
概括
化疗可以通过改变正常细胞来意外地促进癌症的扩散. 针对BCL-xL等特定蛋白质显示出预防这种治疗诱导的瘤生长的希望,但需要进一步的研究.
科学领域:
- 在瘤学瘤学.
- 癌症生物学 癌症生物学
- 细胞衰老 细胞衰老
背景情况:
- 扩散的瘤细胞往往进入休眠状态,对化疗产生抗性.
- 系统化疗可能会导致正常组织损伤,可能会影响癌症的进展.
研究的目的:
- 调查前期化疗如何影响转移殖民和脱发.
- 探索衰老纤维细胞和衰老相关分泌表型 (SASP) 在化疗诱导的前瘤效应中的作用.
- 评估向BCL-xL在减轻这些影响方面的有效性.
主要方法:
- 利用多个小鼠和人类乳腺癌模型.
- 在化疗治疗的纤维细胞进行了体外实验.
- 进行了体内研究,以评估SASP表达和衰老细胞积累.
- 研究了BCL-xL抑制剂对化疗增强转移的影响.
主要成果:
- 在癌症模型中,先前的化疗管理增强了转移性殖民化和外生长.
- 在体外,化疗诱导的纤维细胞衰老和SASP对BCL-xL抑制敏感.
- 在体内,化疗在正常组织中诱导了SASP,但BCL-xL抑制剂没有减少化疗增强的转移,这表明 stromal 细胞中的替代生存机制.
结论:
- 奇怪的是,化疗可以通过改变瘤微环境来促进癌症转移.
- 衰老的 stromal 细胞在化疗后为支持瘤的环境做出了贡献.
- 向BCL-xL不足以在体内克服化疗增强的转移,这表明需要替代治疗策略来管理治疗诱导的正常组织损伤.
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