Institute of Developmental Biology and Cancer Research, CNRS UMR 6543, University of Nice, Centre A. Lacassagne, Nice, France.
J Cell Physiol. 2011 Feb;226(2):299-308. doi: 10.1002/jcp.22400.
A distinguishing phenotype of solid tumors is the presence of an alkaline cellular feature despite the surrounding acidic microenvironment. This phenotypic characteristic of tumors, originally described by Otto Warburg, arises due to alterations in metabolism of solid tumors. Hypoxic regions of solid tumors develop due to poor vascularization and in turn regulate the expression of numerous genes via the transcription factor HIF-1. Ultimately, the tumor microenvironment directs the development of tumor cells adapted to survive in an acidic surrounding where normal cells perish. The provision of unique pH characteristics in tumor cells provides a defining trait that has led to the pursuit of treatments that target metabolism, hypoxia, and pH-related mechanisms to selectively kill cancer cells. Numerous studies over the past decade involving the cancer-specific carbonic anhydrase IX have re-kindled an interest in pH disruption-based therapies. Although an acidification of the intracellular compartment is established as a means to induce normal cell death, the defining role of acid-base disturbances in tumor physiology and survival remains unclear. The aim of this review is to summarize recent data relating to the specific role of pH regulation in tumor cell survival. We focus on membrane transport and enzyme studies in an attempt to elucidate their respective functions regarding tumor cell pH regulation. These data are discussed in the context of future directions for the field of tumor cell acid-base-related research.
实体瘤的一个显著表型特征是存在碱性细胞特征，尽管周围存在酸性微环境。这种肿瘤的表型特征最初是由 Otto Warburg 描述的，它源于实体瘤代谢的改变。由于血管化不良，实体瘤的缺氧区域发展，进而通过转录因子 HIF-1 调节众多基因的表达。最终，肿瘤微环境指导肿瘤细胞的发展，使它们能够适应在正常细胞死亡的酸性环境中生存。肿瘤细胞中提供独特的 pH 特征为治疗提供了一个定义性的特征，这些治疗方法针对代谢、缺氧和 pH 相关机制，以选择性地杀死癌细胞。过去十年中，涉及肿瘤特异性碳酸酐酶 IX 的大量研究重新燃起了人们对基于 pH 破坏的治疗方法的兴趣。尽管细胞内酸化被确立为诱导正常细胞死亡的一种手段，但酸堿平衡紊乱在肿瘤生理学和生存中的明确作用仍不清楚。本综述的目的是总结与肿瘤细胞存活中 pH 调节的特定作用相关的最新数据。我们专注于膜转运和酶的研究，试图阐明它们在肿瘤细胞 pH 调节方面的各自功能。这些数据将在肿瘤细胞酸堿相关研究领域的未来方向方面进行讨论。
