BICC1通过诱导VEGF独立的血管生成来驱动胰腺癌的进展
Chongbiao Huang1, Hui Li1, Yang Xu2
1Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Key Laboratory of Cancer Prevention and Therapy, 300060, Tianjin, China.
Signal transduction and targeted therapy
|July 13, 2023
概括
BICC1通过促进独立于VEGF的血管形成来驱动胰腺癌的生长,从而导致抗VEGF疗法的耐药性. 针对BICC1/LCN2通道提供了一种克服这种阻力的新策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 血管内皮生长因子 (VEGF) 抑制剂通过抑制血管生成对治疗固体瘤至关重要.
- 胰腺管道腺癌 (PAAD) 由于激活了独立于VEGF的益血管性通路,对VEGF抑制剂表现出耐药性.
研究的目的:
- 研究BICC1在PAAD中介导VEGF独立血管生成中的作用.
- 阐明BICC1促进血管生成并赋予抗VEGF治疗的耐药性的分子机制.
- 评估BICC1/LCN2信号作为PAAD中潜在的治疗点.
主要方法:
- 生物信息分析以确定PAAD血管生成中的关键基因.
- 对人类PAAD组织和患者队伍的分析.
- 在体外和体内实验中使用PAAD细胞系和异种移植小鼠模型进行实验.
- 检测RNA结合蛋白质和西方涂抹以研究分子机制.
主要成果:
- 在PAAD组织中,BICC1过度表达,与增加的微血管密度,瘤生长和不良预后相关.
- 在PAAD中,BICC1通过上调利波卡林-2 (LCN2) 表达来促进VEGF独立的血管生成.
- BICC1/LCN2通路激活JAK2/STAT3信号,导致CXCL1的产生和增强的血管生成.
- 在小鼠中,抑制BICC1/LCN2信号减少了瘤生长,并增强了gemcitabine的疗效.
结论:
- BICC1是胰腺癌中VEGF独立血管生成的关键驱动因素,有助于治疗耐药性.
- BICC1/LCN2信号轴代表了克服PAAD抗VEGF耐药性的有前途的治疗标.
- 针对BICC1提供了一种新的策略,以改善胰腺癌患者的治疗结果.
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