PDGFRα控制多个细胞信号,并在瘤进展中起着保护作用
Masao Hayashi1, Noriko Okuno2, Le Thi Thu Trang2
1Department of Pathology, Academic Assembly Faculty of Medicine, University of Toyama, Toyama 930-0194, Japan; Department of Dermatology, Academic Assembly Faculty of Medicine, University of Toyama, Toyama 930-0194, Japan.
概括
瘤细胞中的血小板衍生的生生长因子受体α (PDGFRα) 意外地促进瘤生长和转移. 在瘤细胞中抑制PDGFRα可能提供一种向癌症治疗方法.
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:
- 瘤发育涉及复杂的分子机制,许多方面仍不清楚.
- 血小板衍生生长因子 (PDGF) 和其受体 (PDGFR) 信号通路与癌症进展有关.
研究的目的:
- 研究PDGFRα在瘤进展和转移中的作用.
- 阐明瘤微环境中PDGFRα调节的信号通路.
主要方法:
- 使用了成年PDGFRα条件淘汰 (α-KO) 小鼠植入了易斯肺癌 (LLC) 细胞.
- 分析了瘤生长,肺转移,血管化以及关键信号分子 (PDGF,TGF-α,TGF-β,EGFR,AKT1).
主要成果:
- 与对照组相比,α-KO小鼠的瘤显著扩大,肺转移增加.
- 通过TGF-α激活的LLC细胞中的PDGF-BB-PDGFRα信号,通过EGFR加速了瘤的生长.
- 由于α-KO小鼠血管化不良而导致的缺氧导致TGF-β增加,通过AKT1.1促进肺转移.
结论:
- 间歇细胞中的PDGFRα在瘤进展方面起着保护作用.
- 在瘤细胞中选择性抑制PDGFRα可能是潜在的向癌症治疗.
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