a William Harvey Research Institute, Barts and The London School of Medicine & Dentistry, Queen Mary University of London , London , UK.
b Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham , Birmingham , UK.
Expert Opin Ther Targets. 2018 Sep;22(9):735-743. doi: 10.1080/14728222.2018.1511706. Epub 2018 Sep 3.
Inflammation is associated with the accumulation of lactate at sites of tumor-growth and inflammation. Lactate initiates tissue-responses contributing to disease. We discuss the potential of targeting lactate transporters in the treatment of cancer and inflammatory conditions. Areas covered: Lactate is the end product of glycolysis, often considered a waste metabolite but also a fuel for oxidative cells. It is however an active signaling molecule with immunomodulatory and angiogenic properties. They are the consequence of lactate binding to membrane receptor(s) or being transported through specific carrier-mediated-transporters across the cellular membrane. Carriers are distinct in proton-linked-monocarboxylate-transporters (MCTs) and Na-coupled- electrogenic-transporters, expressed by several tissues including immune-system, endothelium and epithelium. Several tumors and inflammatory sites show accumulation of lactate and altered expression of its transporters, thus suggesting a role of this metabolite in cancer and inflammation. We review the most recent evidence on lactate biology, focusing on transporter expression and function in health and disease. Expert opinion: Lactate-initiated signaling is gaining attention for its implications in cancer and inflammation. This review discusses the therapeutic potential of targeting lactate transporters and drugs that are already in clinical use for cancer and discusses the opportunity to develop new therapeutics for inflammation and cancer.
炎症与肿瘤生长和炎症部位的乳酸积累有关。乳酸会引发组织反应，从而导致疾病。我们讨论了靶向乳酸转运蛋白治疗癌症和炎症性疾病的潜力。
乳酸是糖酵解的终产物，通常被认为是一种废物代谢物，但也是氧化细胞的燃料。然而，它是一种具有免疫调节和血管生成特性的活性信号分子。这些特性是由于乳酸与膜受体结合或通过特定的载体介导转运蛋白穿过细胞膜进行转运所致。载体在质子偶联单羧酸转运蛋白（MCT）和 Na 偶联电致型转运蛋白中是不同的，这些转运蛋白在包括免疫系统、内皮细胞和上皮细胞在内的多种组织中表达。一些肿瘤和炎症部位会积累乳酸并改变其转运蛋白的表达，这表明这种代谢物在癌症和炎症中发挥作用。我们回顾了乳酸生物学的最新证据，重点关注其在健康和疾病中的转运蛋白表达和功能。
乳酸引发的信号转导因其在癌症和炎症中的意义而受到关注。这篇综述讨论了靶向乳酸转运蛋白的治疗潜力，以及已经用于癌症治疗的临床药物，并讨论了为炎症和癌症开发新疗法的机会。
