Exosome-mediated metabolic reprogramming: the emerging role in tumor microenvironment remodeling and its influence on cancer progression

Abstract

Metabolic reprogramming is reported to be one of the hallmarks of cancer, which is an adaptive mechanism by which fast-growing cancer cells adapt to their increasing energy demands. Recently, extracellular vesicles (EVs) known as exosomes have been recognized as crucial signaling mediators in regulating the tumor microenvironment (TME). Meanwhile, the TME is a highly heterogeneous ecosystem incorporating cancer cells, fibroblasts, adipocytes, endothelial cells, mesenchymal stem cells, and extracellular matrix. Accumulated evidence indicates that exosomes may transfer biologically functional molecules to the recipient cells, which facilitate cancer progression, angiogenesis, metastasis, drug resistance, and immunosuppression by reprogramming the metabolism of cancer cells and their surrounding stromal cells. In this review, we present the role of exosomes in the TME and the underlying mechanism of how exosomes exacerbate tumor development through metabolic reprogramming. In addition, we will also discuss the potential role of exosomes targeting metabolic process as biomarkers for tumor diagnosis and prognosis, and exosomes-mediated metabolic reprogramming as potential targets for cancer therapy. Furthermore, a better understanding of the link between exosomes and metabolic reprogramming, and their impact on cancer progression, would provide novel insights for cancer prevention and treatment in the future.

Adaptive Mechanisms of Tumor Therapy Resistance Driven by Tumor Microenvironment

“…Exosomes or extracellular vesicles (EVs) with sizes of 40 to 100 nm, originating from large multivesicular bodies (MVBs), mediate cell-to-cell communication by transferring biologically active cargo, including DNAs, RNAs, proteins, and metabolites ( Schneider and Simons, 2013 ; Sun, 2016 ; Mashouri et al, 2019 ). Exosomes have been demonstrated to be crucial signaling mediators in the TME, participating in tumorigenesis, metastasis, TME remodeling, angiogenesis, and therapeutic resistance ( Figure 4 ) ( Luga et al, 2012 ; Yoshizaki et al, 2013 ; Jeppesen et al, 2014 ; Sung et al, 2015 ; You et al, 2015 ; Paolillo and Schinelli, 2017 ; Wang X. et al, 2018 ; Zeng et al, 2018 ; Mashouri et al, 2019 ; Steinbichler et al, 2019 ; Yang E. et al, 2020 ). For example, exosomes have been found to control metabolic reprogramming ( Yang E. et al, 2020 ).…”

Exosome-mediated communication between tumor cells and tumor-associated macrophages: implications for tumor microenvironment

“…Exosomes might also take part in these metabolic processes. 142 For example, cancer-associated fibroblasts (CAFs) secrete exosomal miR-522 to inhibit ferroptosis in GC cells by targeting arachidonate lipoxygenase 15 (ALOX15) and blocking lipid-ROS accumulation to support tumor progression and drug resistance. 129 However, whether TAM-derived exosomes are involved in these processes is unknown and requires in-depth study.…”

Integrin Regulation in Immunological and Cancerous Cells and Exosomes

“…Tumor endothelial cells and cancer cells are important components of the tumor microenvironment. Their metabolic cross-talk, dynamic interaction and competition for nutrients influence the progression of cancer [ 140 ]. Cancer cells use massive amounts of glucose for their proliferation and survival.…”