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随机上皮层-介质细胞转换使非癌性肺细胞行为多样化
Sugandha Bhatia1, Jennifer H Gunter2, Joshua T Burgess1
1Queensland University of Technology (QUT), School of Biomedical Sciences, Centre for Genomics and Personalised Health at the Translational Research Institute, Woolloongabba 4102, QLD, Australia.
Translational oncology
|August 23, 2023
概括
非癌症的人类肺细胞可以自发地获得类似癌症的特征,如转移潜力,没有遗传变化. 这种上皮层-介质细胞可塑性 (EMP) 突出显示了癌前状态.
科学领域:
- 细胞生物学 细胞生物学
- 癌症研究 癌症研究
- 发育生物学是发展生物学.
背景情况:
- 表皮介质可塑性 (EMP) 是癌症的一个关键过程,驱动入侵,转移和治疗耐药性.
- EMP允许细胞在上皮和介质细胞状态之间过渡,改变它们的形态和功能.
研究的目的:
- 为了研究非癌性上皮细胞是否可以在没有遗传改变的情况下表现出EMP.
- 描述与人类肺细胞中自发EMP相关的表型和分子变化.
主要方法:
- 培养近二倍体,非癌症的人类上皮质肺细胞.
- 产生单细胞衍生克隆来评估表型可塑性.
- 使用形态学,分子学和功能学分析,表皮状和介质状克隆的特征.
- 分析干性标记物表达和代谢概况.
- 使用3D细胞培养模型.
主要成果:
- 自发性EMP发生在没有遗传变化的非癌症人类肺上皮细胞中.
- 超过一半的单细胞基因克隆采用了中细胞形态.
- 介质细胞克隆表现出上皮标记的丧失,细胞形状的改变和运动能力的降低,与基本不变的增殖.
- 干部和代谢重新连接是独立于细胞表型的变化.
- 皮质克隆在3D培养中显示出介质过渡的增加.
结论:
- 在基因改变之前,非癌性上皮细胞可以通过EMP获得与癌症相关的转移性特征.
- 这种可塑性代表了潜在的癌前状态,为早期癌症发展提供了新的见解.
- 非癌细胞中的EMP可能是启动癌症进展的关键因素.
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