在癌症生长和转移中,RNA Aptamer针对Adam8进行向
Zhiyong Mi1, Marissa C Kuo2, Paul C Kuo1
1Department of Surgery, University of South Florida, Tampa, FL 33620, USA.
Cancers
|June 28, 2023
概括
通过使用RNA吸收酶的分解蛋白和金属蛋白酶8 (Adam8) 阻断,通过阻断癌症相关纤维细胞的维持来抑制癌症干和转移. 这揭示了与癌症相关的纤维细胞启动和维护的独特途径.
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 癌症的进展包括由细胞信号调节的转移支持的变化.
- 分解蛋白和金属蛋白酶8 (Adam8) 是一种由炎症刺激诱导的糖蛋白.
- 肌纤维细胞样癌症相关纤维细胞 (myCAF) 诱导癌症干,这对它们自身的维持至关重要.
研究的目的:
- 研究Adam8在癌症干细胞和myCAF表型中的作用.
- 开发一种针对Adam8的治疗策略,以抑制癌症的进展.
主要方法:
- 在与myCAF共同培养的MDA-MB-231细胞中,确定Adam8是一种sox2依赖蛋白.
- 开发了一种RNA吸收酶 (Adam8-Apt1-26nt),用于阻断可溶的Adam8.
- 利用异种移植模型和流细胞计量来评估瘤生长,转移和myCAF分数.
主要成果:
- 亚当8被确定为由myCAF介导的癌症干引起的分泌蛋白质.
- 亚当8-Apt1-26nt治疗阻止了myCAF表型的维持,降低了癌症干性.
- 在异种移植模型中,Adam8-Apt1-26nt的使用减少了瘤生长和转移.
- 流细胞计显示治疗后myCAF分数下降.
结论:
- 可溶性Adam8在维护myCAF表型方面发挥着关键作用,与启动它的途径不同.
- 用阿普坦酶准Adam8提供了一种潜在的治疗方法,可以抑制癌症的进展和转移.
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