衰老的血管内皮细胞通过补体C3激活促进口腔状细胞癌的进展
Fangqi Jing1, Jingtian Mu2, Junjiang Liu2
1State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China.
Archives of oral biology
|March 30, 2025
概括
衰老的血管内皮细胞 (VEC) 通过激活补体C3.3,促进口腔状细胞癌 (OSCC) 的生长. 向补充C3为OSCC提供了潜在的新疗法.
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
背景情况:
- 瘤微环境 (TME) 影响癌症的进展和治疗反应.
- 已知衰老的 stromal 细胞可以促进瘤生长.
- 在口腔状细胞癌 (OSCC) 中衰老的血管内皮细胞 (VEC) 的作用尚不清楚.
研究的目的:
- 调查老化VEC对OSCC进展的影响.
- 阐明老化VECs影响OSCC的潜在机制.
主要方法:
- 使用西斯普拉丁诱导VEC衰老.
- 评估衰老标记 (SA-β-gal,p16,p21,p53) 和细胞功能 (增殖,迁移,入侵).
- RNA测序,免疫组织化学和异种移植小鼠模型,以探索与衰老相关的分泌表型和分子通路,专注于补充C3.
主要成果:
- 西斯普拉丁诱导的衰老VEC表现出特有的衰老标志物和减少的增殖/迁移.
- 衰老的VEC显著增强了OSCC细胞的增殖,迁移和入侵.
- 这种促进是由补充C3的激活介导的,在老化的VEC中观察到C3水平的增加.
- 抑制补充C3有效地减少了OSCC细胞的增殖和侵入,无论是体外还是体内.
结论:
- 由青诱导的衰老性VECs通过补体C3激活加速OSCC的进展.
- 在衰老的VEC中准C3补充剂为OSCC治疗提供了一个有希望的治疗途径.
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