乳酸:肿瘤环境中的代谢驱动力 Lactate: A Metabolic Driver in the Tumour Landscape 


佛罗伦萨大学实验与临床生物医学科学系，意大利佛罗伦萨50134
2018年11月22日在线。


要点
在肿瘤环境中，乳酸不再被认为是发酵细胞代谢的废物，而是作为一种强大的分子，影响周围每个细胞的行为，并被吸收到肿瘤中。

乳酸在癌细胞和非恶性细胞之间或癌细胞之间建立代谢耦合，从而维持肿瘤生长。

乳酸在抑制肿瘤部位大量免疫细胞介导的免疫监测中起着关键作用。

环境乳酸根据细胞亚型及其特定的转运体/受体触发信号激活。

以乳酸代谢和转运为靶点是一种很有前途的肿瘤治疗方法。

长期以来，人类肿瘤中乳酸的存在一直被忽视，仅把它作为糖酵解产生的废物和作为恶性肿瘤的生物标志物。最近，乳酸被重新发现作为信号分子，在肿瘤微环境中调控代谢途径、免疫反应和细胞间通讯中发挥重要作用。本文综述了近年来关于乳酸在肿瘤和肿瘤相关细胞的行为和表型形成中的功能作用的发现，并描述了在肿瘤中靶向乳酸转运和代谢的潜在临床方法。
　

关键字
线粒体 瘤-间质瘤相互作用 肿瘤微环境 肿瘤代谢

Lactate: A Metabolic Driver in the Tumour Landscape Author links open overlay panelLuigiIppolito1AndreaMorandi1ElisaGiannoni1PaolaChiarugi1 1 Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50134 Florence, Italy Available online 22 November 2018. crossmark-logo Show less https://doi.org/10.1016/j.tibs.2018.10.011Get rights and content Highlights In a tumour environment, lactate is no longer considered as a waste product from fermentative cell metabolism but instead as a powerful molecule that affects the behaviour of each cell surrounding and recruited to the tumour. Lactate establishes metabolic coupling between cancer cells and non-malignant cells, or among cancer cells themselves, thereby sustaining tumour growth. Lactate plays a key role in dampening immunosurveillance mediated by a plethora of immune cells recruited to the tumour site. Environmental lactate triggers signalling activation according to the cell subtype and its specific transporters/receptors. Targeting lactate metabolism and transport is a promising approach for cancer therapeutics. The presence of lactate in human tumours has been long neglected, confined to the role of a waste product derived from glycolysis and as a biomarker of malignancy. More recently, lactate has been rediscovered as signalling molecule that plays important roles in the regulation of the metabolic pathways, the immune response, and cell-to-cell communication within the tumour microenvironment. This review examines recent discoveries about the functional role of lactate in shaping the behaviour and the phenotype of tumour and tumour-associated cells, and describes potential clinical approaches to target lactate transport and metabolism in tumours. Previous article in issueNext article in issue Keywords mitochondriatumour–stroma interplaytumour microenvironmenttumour metabolism
　

参考文献

Lactate: A Metabolic Driver in the Tumour Landscape - ScienceDirecthttps://www.sciencedirect.com/science/article/abs/pii/S0968000418302275

Metabolic changes associated with tumor metastasis, part 1: tumor pH, glycolysis and the pentose phosphate pathway | ISCaM - International Society of Cancer Metabolism https://www.iscams.org/paper/metabolic-changes-associated-tumor-metastasis-part-1-tumor-ph-glycolysis-and-pentose-phosphate