ECM组成不同调节正常和癌症胰腺管道上皮细胞中的细胞内和细胞外pH值
Daria Di Molfetta1, Stefania Cannone1, Maria Raffaella Greco1
1Department of Biosciences, Biotechnology and Environment, University of Bari Aldo Moro, 70126 Bari, Italy.
International journal of molecular sciences
|July 14, 2023
概括
胰腺癌细胞表现出改变的细胞内pH (pHi) 调节,受细胞外基质 (ECM) 的影响. 富含原-I的ECM逆转了酸平衡,影响瘤进展中的pHi平衡.
科学领域:
- 细胞生物学 细胞生物学
- 在瘤学瘤学.
- 生理学 生理学 生理学
背景情况:
- 细胞内pH (pHi) 调节对外分胰腺功能至关重要,涉及像Na+/H+交换机异形1 (NHE1) 这样的离子载体.
- 在胰腺管腺癌 (PDAC) 中观察到pHi和NHE1的失调.
- 富含原I的细胞外基质 (ECM) 在PDAC进展过程中加剧了间歇性酸化.
研究的目的:
- 调查休息时的pHi,pHi对NaHCO3和酸化的反应,以及NHE1在pHi调节中的作用.
- 为了比较正常的人类胰腺细胞 (HPDE),癌症辅酶细胞 (CPC) 和癌症干细胞 (CSC) 的pHi调节.
- 评估ECM组成对PDAC模型中的pHi稳态的影响.
主要方法:
- 在模拟ECM变化的矩阵上对HPDE,CPC和CSC的器官类型培养.
- 测量休息时的pHi和从酸载荷中恢复的pHi.
- 评估Na+/H+交换器异型1 (NHE1) 活性对细胞外NaHCO3.3的反应.
主要成果:
- 在生理ECM上,HPDE细胞表现出最性pHi;在癌细胞中,富含原I的ECM会逆转这种平衡.
- 细胞外NaHCO3降低了静止pHi和pHi恢复,特别是在正常ECM上的HPDE细胞中.
- 与正常细胞相比,癌细胞NHE1活动对细胞外NaHCO3的敏感性较低.
结论:
- ECM的组成显著影响胰腺细胞中的pHi稳态.
- 瘤微环境,包括ECM和细胞外pH (pHe) 波动,使pHi倾向于瘤中见到的NaHCO3梯度.
- 在PDAC微环境中,NHE1在pHi调节中起着差异性作用.
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