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布拉迪基宁B1受体影响与瘤相关的巨细胞活动和质母细胞瘤进展
Ching-Kai Shen1, Bor-Ren Huang2,3, Vichuda Charoensaensuk4
1Graduate Institute of Biomedical Science, China Medical University, Taichung 40402, Taiwan.
Antioxidants (Basel, Switzerland)
|August 26, 2023
概括
在质母细胞瘤 (GBM) 中过度表达布拉迪基宁B1受体 (B1R) 会增强瘤生长和免疫逃避. B1R促进迁移,入侵和巨细胞活动,这表明它是GBM的治疗目标.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 布拉迪基宁B1受体 (B1R) 是一种炎症媒介,与癌症有关.
- B1R促进质母细胞瘤 (GBM) 细胞迁移和入侵.
- B1R对瘤相关巨细胞 (TAM) 和GBM进展的影响机制尚不清楚.
研究的目的:
- 研究GBM中B1R过度表达 (OE) 对瘤相关免疫细胞和GBM进展的调控作用.
主要方法:
- 在GBM中构建了B1R野生类型等离子体,并开发了B1ROE模型.
- 评估了细胞粘附分子 (ICAM-1,VCAM-1),细胞因子,化学因子,CD68,血氧酶-1和编程死亡配体1的表达.
- 评估了GBM细胞迁移,单细胞附着和活性氧物种水平.
- 利用内外移植的小鼠模型来评估瘤生长和存活率.
主要成果:
- 在GBM中B1ROE增加了ICAM-1,VCAM-1,IL-6,IL-8,CXCL11,CCL5的表达,增强了GBM细胞迁移和单细胞附着.
- B1R OE增加了TAMs中的CD68表达和上调的血氧酶-1,减少了活性氧物种,并保护GBM细胞免受氧化应激.
- 在GBM细胞和巨细胞中,B1R OE提高了编程死亡配体1的调节,赋予了对T细胞反应的抵抗力,并促进了瘤生长,在体内生存率降低.
结论:
- 在GBM中B1R表达促进了TAM活动,并通过各种机制调节了GBM的进展.
- B1R影响GBM细胞粘附,迁移,免疫细胞招募,氧化应激和免疫逃避.
- B1R代表GBM治疗的潜在治疗标.
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