Section for Cell Biology and Physiology, Department of Biology, Faculty of Science, University of Copenhagen, Universitetsparken 13, 2100, Copenhagen, Denmark.
Pflugers Arch. 2024 Apr;476(4):689-701. doi: 10.1007/s00424-024-02918-z. Epub 2024 Feb 9.
The copious metabolic acid production and -extrusion by cancer cells render poorly vascularized regions of solid tumors highly acidic. A growing list of proton - and bicarbonate transporters has been suggested to contribute to net acid extrusion from cancer cells, and/or been shown to be dysregulated and favor malignant development in various cancers. The great majority of these roles have been studied at the level of the cancer cells. However, recent advances in understanding of the cellular and physicochemical heterogeneity of solid tumors both enable and necessitate a reexamination of the regulation and roles of acid-base transporters in such malignancies. This review will briefly summarize the state-of-the-art, with a focus on the SLC9A and SLC4A families, for which most evidence is available. This is followed by a discussion of key concepts and open questions arising from recent insights and of the challenges that need to be tackled to address them. Finally, opportunities and challenges in therapeutic targeting of the acid-base transportome in cancers will be addressed.
癌细胞大量产生和排出代谢酸，使实体瘤中血管生成不良的区域高度酸化。越来越多的质子和碳酸氢盐转运蛋白被认为有助于癌细胞净酸排出，并且/或者在各种癌症中被证明失调并有利于恶性发展。这些作用中的绝大多数已在癌细胞水平上进行了研究。然而，对实体瘤细胞和物理化学异质性的理解的最新进展既使重新检查酸碱转运体在这些恶性肿瘤中的调节和作用成为可能，也使之成为必要。这篇综述将简要总结最新进展，重点介绍 SLC9A 和 SLC4A 家族，因为这些家族有最多的证据。接下来将讨论最近的研究结果所产生的关键概念和悬而未决的问题，以及解决这些问题所需要应对的挑战。最后，将讨论在癌症中靶向酸碱转运体组的治疗机会和挑战。
