维持血管平衡的RGS5被瘤微环境所改变
Peng Kong1, Xu Wang1,2, Ya-Kun Gao1
1Department of Biochemistry and Molecular Biology, College of Basic Medicine, Key Laboratory of Neural and Vascular Biology of Ministry of Education, Key Laboratory of Medical Biotechnology of Hebei Province, Hebei Medical University, Shijiazhuang, China.
Biology direct
|November 21, 2023
概括
调节G蛋白信号传递5 (RGS5) 通常可以预防血管炎症,但在乳腺瘤中会促进血管炎症. 瘤环境改变RGS5的功能,有助于癌症的进展和转移.
科学领域:
- 血管生物学 血管生物学
- 在瘤学瘤学.
- 细胞信号传递 细胞信号传递
背景情况:
- 调节G蛋白信号传递5 (RGS5) 在血管光滑肌细胞 (VSMC) 和细胞周细胞中高度表达.
- RGS5负面调节G蛋白结合受体 (GPCR) 信号传递,并影响VSMC表型和瘤血管重塑.
- 它在正常与瘤血管重塑中的确切作用仍然存在争议.
研究的目的:
- 研究RGS5在血管炎症和重塑中的功能意义.
- 确定RGS5在乳腺癌组织中的表达及其在瘤血管化中的作用.
- 阐明乳腺癌细胞条件介质如何影响VSMC表型.
主要方法:
- 在VSMC中利用RGS5淘汰赛小鼠和腺相关病毒 (AAV) 介导的体内RGS5操纵.
- 在三阴性乳腺癌 (TNBC) 和非TNBC组织中通过免疫光和免疫组织化学评估RGS5表达.
- 在暴露于乳腺癌细胞受条件介质 (BC-CM) 后,使用 fagocytic 活性试验,粘附试验和西部斑分析评估了 VSMC 亲炎性表型.
主要成果:
- 由于RGS5的缺陷加剧了VSMC的积累和热,导致血管重塑,而RGS5的过度表达反转了这种情况.
- 在乳腺癌中,RGS5表达在TNBC组织和瘤血管系统中升高,与血管网络增加相关.
- BC-CM诱导了一种亲炎性和粘性VSMC表型,有瘤衍生的RGS5转移到VSMC的证据.
结论:
- 瘤微环境将RGS5从抗炎媒介重新编程为促炎媒介.
- 瘤诱导的RGS5促进了一种亲炎性VSMC表型,该表型支持瘤转移.
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