胰岛素样生长因子1受体通过β-1整合素调节乳腺癌细胞粘附
Christopher A Galifi1, Elvan Dogan1, Luis Fernandez Almansa1
1Department of Pharmacology, Physiology, & Neuroscience, Center for Cell Signaling and Cancer Institute of New Jersey, New Jersey Medical School, Rutgers Health, Newark, NJ, USA.
胰岛素样生长因子1 (IGF-1) 的刺激和其受体 (IGF1R) 的抑制都会增加三阴性乳腺癌 (TNBC) 细胞粘附. 这表明表面结合的IGF1R抑制了细胞粘附,为TNBC转移提供了洞察力.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 胰岛素样生长因子 (IGF-1/IGF1R) 途径与乳腺癌的攻击性有关.
- 在临床试验中以前试图抑制这种途径的尝试失败了,这突显了对其在三阴性乳腺癌 (TNBC) 转移中的作用的理解上的差距.
- 最近的研究表明,IGF1R影响整合素功能和癌细胞粘附动态.
研究的目的:
- 调查IGF1R直接调节癌细胞粘附的假设.
- 阐明IGF1R影响TNBC细胞粘附的机制.
- 探索IGF1R在TNBC细胞对内皮细胞的粘附中的作用.
主要方法:
- 使用了MDA-MB-231和HS578TTNBC细胞系.
- 采用siRNA介导的IGF1R和整体素的淘汰.
- 进行了粘附测试,包括xCELLigence E板,以量化在各种条件下 (IGF-1刺激,IGF1R敲击) 细胞粘附.
- 评估了对人类静脉内皮细胞 (HUVECs) 的粘附性.
主要成果:
- IGF-1刺激增强了MDA-MB-231 TNBC细胞粘附,这种效应被IGF1R抑制剂和受体内化抑制剂逆转.
- 意想不到的是,IGF1R的抑制也显著增加了细胞粘附.
- 同时降低β1整合素逆转了IGF-1刺激和IGF1R降低时观察到的增强粘附,表明β1整合素依赖.
- 抑制IGF1R信号传递减少了TNBC细胞对HUVECs的粘附.
结论:
- 矛盾的是,IGF-1刺激和IGF1R淘汰都促进TNBC细胞粘附.
- 一个拟议的模型表明,表面结合的IGF1R抑制β1整合素功能,从而阻断细胞粘附.
- 由质介导的IGF1R内部化对其对粘附的影响至关重要.
- 这些发现可能解释了在临床试验中选择性IGF1R抗剂缺乏成功.
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