时空pH异质性作为癌症进展和治疗抗性的促进因素

Korenchan David E, Flavell Robert R

Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA 94143, USA.

Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94143, USA.

Cancers (Basel). 2019 Jul 20;11(7):1026. doi: 10.3390/cancers11071026.

Dysregulation of pH in solid tumors is a hallmark of cancer. In recent years, the role of altered pH heterogeneity in space, between benign and aggressive tissues, between individual cancer cells, and between subcellular compartments, has been steadily elucidated. Changes in temporal pH-related processes on both fast and slow time scales, including altered kinetics of bicarbonate-CO exchange and its effects on pH buffering and gradual, progressive changes driven by changes in metabolism, are further implicated in phenotypic changes observed in cancers. These discoveries have been driven by advances in imaging technologies. This review provides an overview of intra- and extracellular pH alterations in time and space reflected in cancer cells, as well as the available technology to study pH spatiotemporal heterogeneity.

实体瘤中pH值的失调是癌症的一个标志。近年来，pH值在空间上的异质性变化，在良性组织和侵袭性组织之间、单个癌细胞之间以及亚细胞区室之间的作用，已逐渐被阐明。在快速和慢速时间尺度上与pH值相关的时间过程的变化，包括碳酸氢盐-CO交换动力学的改变及其对pH缓冲的影响，以及由代谢变化驱动的渐进性变化，进一步与癌症中观察到的表型变化有关。这些发现得益于成像技术的进步。本综述概述了癌细胞中细胞内和细胞外pH值在时间和空间上的变化，以及研究pH值时空异质性的现有技术。