与癌症相关的纤维细胞衍生物CXCL14通过增强膀癌中核酸切除修复来驱动基抗药性
在PubMed上查看摘要
概括
此摘要是机器生成的。癌症相关纤维细胞 (CAF) 在膀癌中驱动化疗抵抗. 用抑制剂向CXCL14-CCR7-STAT3通路可以克服耐药性并改善治疗结果.
科学领域
- 癌症学
- 癌症生物学
- 瘤微环境研究
背景情况
- 主要化学抵抗是治疗膀癌的一个主要障碍.
- 在瘤微环境 (TME) 中,与癌症相关的纤维细胞 (CAF) 显著促进药物耐药性.
- 通过CAF诱导化学抵抗的确切分子机制尚未完全理解.
研究的目的
- 阐明CAFs在膀癌中诱导化学抵抗的分子机制.
- 确定参与化学抵抗的CAF衍生的关键分泌因子.
- 评估针对CAF介导途径的治疗潜力.
主要方法
- 从膀癌组织和相邻的正常组织中分离初级纤维细胞.
- 生物信息学分析,RT-qPCR和双露西法酶报告测试用于研究CXCL14.
- 在体外和体内模型,包括患者衍生的有机物 (PDO),以评估西斯的敏感性和治疗向性.
主要成果
- 来自抗西斯的患者的CAF显示出增强的膜化疗抵抗诱导.
- 通过CAF分泌的CXCL14激活了癌细胞中的CCR7- STAT3信号,提高了DNA修复基因ERCC4的调节,并促进了对西斯普拉丁的抗药性.
- 抑制CCR7或STAT3逆转了化学阻力,增强了思的疗效,并揭示了涉及代谢重编程的反循环.
结论
- 在膀癌中,CXCL14/CCR7/STAT3轴是思素耐药性的关键介质.
- 这一途径影响了DNA修复和糖解代谢.
- 与西斯普拉丁和CCR7或STAT3抑制剂的联合治疗有望克服化疗抵抗.
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