Acidic metabolic waste products accumulate in the tumor microenvironment because of high metabolic activity and insufficient perfusion. In tumors, the acidity of the interstitial space and the relatively well-maintained intracellular pH influence cancer and stromal cell function, their mutual interplay, and their interactions with the extracellular matrix. Tumor pH is spatially and temporally heterogeneous, and the fitness advantage of cancer cells adapted to extracellular acidity is likely particularly evident when they encounter less acidic tumor regions, for instance, during invasion. Through complex effects on genetic stability, epigenetics, cellular metabolism, proliferation, and survival, the compartmentalized pH microenvironment favors cancer development. Cellular selection exacerbates the malignant phenotype, which is further enhanced by acid-induced cell motility, extracellular matrix degradation, attenuated immune responses, and modified cellular and intercellular signaling. In this review, we discuss how the acidity of the tumor microenvironment influences each stage in cancer development, from dysplasia to full-blown metastatic disease.

中文翻译：

---

酸性肿瘤微环境是癌症的驱动因素。

由于代谢活性高和灌注不足，酸性代谢废物积聚在肿瘤微环境中。在肿瘤中，间隙空间的酸度和相对良好维持的细胞内pH值会影响癌症和基质细胞功能，它们的相互作用以及它们与细胞外基质的相互作用。肿瘤的pH值在空间和时间上是异质的，适应癌细胞外酸性的癌细胞在适应性方面的优势可能特别明显，例如当它们在入侵过程中遇到酸性较低的肿瘤区域时。通过对遗传稳定性，表观遗传学，细胞代谢，增殖和存活的复杂影响，分隔的pH微环境有利于癌症的发展。细胞选择加剧了恶性表型，酸诱导的细胞运动，细胞外基质降解，减弱的免疫应答以及修饰的细胞和细胞间信号转导进一步增强了这种作用。在这篇综述中，我们讨论了肿瘤微环境的酸度如何影响从发育异常到成熟的转移性疾病的癌症发展的每个阶段。