Department of Oral Function and Molecular Biology, Ohu University School of Dentistry, 963-8611, Koriyama, Japan.
Cancer Cell Int. 2013 Sep 3;13(1):89. doi: 10.1186/1475-2867-13-89.
Acidic extracellular pH is a major feature of tumor tissue, extracellular acidification being primarily considered to be due to lactate secretion from anaerobic glycolysis. Clinicopathological evidence shows that transporters and pumps contribute to H+ secretion, such as the Na+/H+ exchanger, the H+-lactate co-transporter, monocarboxylate transporters, and the proton pump (H+-ATPase); these may also be associated with tumor metastasis. An acidic extracellular pH not only activates secreted lysosomal enzymes that have an optimal pH in the acidic range, but induces the expression of certain genes of pro-metastatic factors through an intracellular signaling cascade that is different from hypoxia. In addition to lactate, CO2 from the pentose phosphate pathway is an alternative source of acidity, showing that hypoxia and extracellular acidity are, while being independent from each other, deeply associated with the cellular microenvironment. In this article, the importance of an acidic extracellular pH as a microenvironmental factor participating in tumor progression is reviewed.
酸性的细胞外 pH 是肿瘤组织的一个主要特征，细胞外酸化主要归因于无氧糖酵解产生的乳酸分泌。临床病理证据表明，转运体和泵也有助于 H+的分泌，如 Na+/H+交换器、H+-乳酸协同转运体、单羧酸转运体和质子泵（H+-ATP 酶）；这些也可能与肿瘤转移有关。酸性的细胞外 pH 不仅激活了具有最佳 pH 值在酸性范围内的分泌溶酶体酶，还通过与缺氧不同的细胞内信号级联诱导某些促转移因子基因的表达。除了乳酸，戊糖磷酸途径产生的 CO2 也是酸度的另一个来源，这表明缺氧和细胞外酸度虽然相互独立，但与细胞微环境密切相关。本文综述了细胞外酸性 pH 值作为参与肿瘤进展的微环境因素的重要性。
