Yang Hao, Wang Jingyi, Huang Gang
Shanghai Key Laboratory of Molecular Imaging, Jiading District Central Hospital Affiliated Shanghai University of Medicine and Health Sciences, Shanghai, China.
Department of Nuclear Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
Front Pharmacol. 2022 Dec 16;13:1009952. doi: 10.3389/fphar.2022.1009952. eCollection 2022.
Warburg effect is characterized by excessive consumption of glucose by the tumor cells under both aerobic and hypoxic conditions. This metabolic reprogramming allows the tumor cells to adapt to the unique microenvironment and proliferate rapidly, and also promotes tumor metastasis and therapy resistance. Metabolic reprogramming of tumor cells is driven by the aberrant expression and activity of metabolic enzymes, which results in the accumulation of oncometabolites, and the hyperactivation of intracellular growth signals. Recent studies suggest that tumor-associated metabolic remodeling also depends on intercellular communication within the tumor microenvironment (TME). Small extracellular vesicles (sEVs), also known as exosomes, are smaller than 200 nm in diameter and are formed by the fusion of multivesicular bodies with the plasma membrane. The sEVs are instrumental in transporting cargoes such as proteins, nucleic acids or metabolites between the tumor, stromal and immune cells of the TME, and are thus involved in reprogramming the glucose metabolism of recipient cells. In this review, we have summarized the biogenesis and functions of sEVs and metabolic cargos, and the mechanisms through they drive the Warburg effect. Furthermore, the potential applications of targeting sEV-mediated metabolic pathways in tumor liquid biopsy, imaging diagnosis and drug development have also been discussed.
瓦伯格效应的特征是肿瘤细胞在有氧和缺氧条件下都会过度消耗葡萄糖。这种代谢重编程使肿瘤细胞能够适应独特的微环境并迅速增殖,还会促进肿瘤转移和治疗抗性。肿瘤细胞的代谢重编程由代谢酶的异常表达和活性驱动,这会导致致癌代谢物的积累以及细胞内生长信号的过度激活。最近的研究表明,肿瘤相关的代谢重塑还取决于肿瘤微环境(TME)内的细胞间通讯。小细胞外囊泡(sEVs),也称为外泌体,直径小于200nm,由多囊泡体与质膜融合形成。sEVs有助于在TME的肿瘤、基质和免疫细胞之间运输蛋白质、核酸或代谢物等货物,因此参与重编程受体细胞的葡萄糖代谢。在这篇综述中,我们总结了sEVs和代谢货物的生物发生和功能,以及它们驱动瓦伯格效应的机制。此外,还讨论了靶向sEV介导的代谢途径在肿瘤液体活检、成像诊断和药物开发中的潜在应用。
Front Pharmacol. 2022-12-16
Cell Commun Signal. 2023-5-19
Cytokine Growth Factor Rev. 2023-10
J Exp Clin Cancer Res. 2023-3-10
Cancers (Basel). 2021-8-30
Cytokine Growth Factor Rev. 2021-10
Cell Death Dis. 2022-2-2