细胞代谢重编程是肿瘤细胞的主要特征,其对于肿瘤发生、生长、转移以及维持自身在不利条件下的存活至关重 要。 肿瘤细胞通过“有氧糖酵解”大量产生乳酸并释放至胞外,导致乳酸在肿瘤微环境累积并使其呈现低 pH 值特征。 近年 来,大量研究表明肿瘤微环境中的乳酸不仅可以作为能源物质被肿瘤细胞摄取利用,并且对肿瘤细胞、多种免疫细胞与基质 细胞具有重要调控作用。 总体上,乳酸通过多重机制对肿瘤微环境中的不同组分产生不同影响。 一方面,乳酸通过介导肿瘤 细胞代谢重编程、信号转导或表观遗传修饰直接增强肿瘤细胞的存活、增殖与迁移能力。 另一方面,乳酸可介导血管生成、 “免疫逃逸”等过程间接促进肿瘤发生、生长与转移。 并且,乳酸相关代谢酶、转运体及其下游调控靶点均与肿瘤发展密切相 关,具有被开发为肿瘤治疗靶向药物的潜力。 本文总结了近期关于肿瘤微环境中乳酸的功能及其机制研究,并对其作为肿瘤 治疗靶点的前景及未来的研究方向进行探讨。

Metabolic reprogramming is a major hallmark of tumor cells. It is vital for tumor tumorigenesis growth metastasis and survival in adverse condition. Tumor cells abundantly produce lactic acid via 􀆵 aerobic glycolysis and released to extracellular microenvironment. This causes lactic acid to accumulate in the tumor microenvironment and makes it in low pH value. Recent studies revealed that lactic acid can not only be utilized as energy resources by tumor cells but also play regulated roles in tumor cells immune cells and stroma cells. In general lactic acid plays different roles in different components of tumor microenvironment. On the one hand lactic acid directly enhances the survival proliferation or migration of tumor cells by mediating metabolic reprogramming signal transduction or epigenetic modification. On the other hand lactic acid promotes tumor formation growth or metastasis indirectly by mediating angiogenesis or immune escape. In addition lactic acid - related metabolic enzymes transporters and its downstream targets significantly correlates with tumor progression which have the potential to be targeted drugs in cancer therapy. This review summarizes the recent advances in the function and mechanism of lactic acid in tumor microenvironment and discusses the future research orientation and its prospect as tumour therapeutic targets.