bims-exocan Biomed News
on Exosomes roles in cancer
Issue of 2023–03–12
thirteen papers selected by
Muhammad Rizwan, COMSATS University
  1. Exosomes in Colorectal Cancer: From Physiology to Clinical Applications.
  2. Extracellular Vesicle-DNA: The Next Liquid Biopsy Biomarker for Early Cancer Diagnosis?
  3. Unraveling the significance of exosomal circRNAs in cancer therapeutic resistance.
  4. Exosomal microRNAs in cancer: Potential biomarkers and immunotherapeutic targets for immune checkpoint molecules.
  5. [Research progress and clinical application value of exosomal circRNAs in hepatocellular carcinoma].
  6. Loss of exosomal miR-200b-3p from hypoxia cancer-associated fibroblasts promotes tumorigenesis and reduces sensitivity to 5-Flourouracil in colorectal cancer via upregulation of ZEB1 and E2F3.
  7. Hepatocellular Carcinoma Cell-Derived Exosomal miR-21-5p Induces Macrophage M2 Polarization by Targeting RhoB.
  8. The BAP31/miR-181a-5p/RECK axis promotes angiogenesis in colorectal cancer via fibroblast activation.
  9. Exosomal ZFPM2-AS1 contributes to tumorigenesis, metastasis, stemness, macrophage polarization, and infiltration in hepatocellular carcinoma through PKM mediated glycolysis.
  10. Long Non-Coding RNAs Within Macrophage-Derived Exosomes Promote BMSC Osteogenesis in a Bone Fracture Rat Model.
  11. Exosomal Mir-3613-3p derived from oxygen-glucose deprivation-treated brain microvascular endothelial cell promotes microglial M1 polarization.
  12. Exosomal miR-21-5p derived from multiple myeloma cells promote renal epithelial-mesenchymal transition through targeting TGF-β/SMAD7 signaling pathway.
  13. Exosomal cargos-mediated metabolic reprogramming in tumor microenvironment.
  1. Int J Mol Sci. 2023 Feb 23. pii: 4382. [Epub ahead of print]24(5):
    Exosomes in Colorectal Cancer: From Physiology to Clinical Applications.
    Stefan Titu, Vlad Alexandru Gata, Roxana Maria Decea, Teodora Mocan, Constantin Dina, Alexandru Irimie, Cosmin Ioan Lisencu.
      Exosomes are nanosized vesicles that have been found to be involved in many diseases. Exosomes can mediate communication between cells in a variety of ways. Certain types of mediators derived from cancer cells can play a crucial role in the development of this pathology, promoting tumor growth, invasion, metastasis, angiogenesis, and immunomodulation. Exosomes in the bloodstream show promise as a future tool for detecting cancer at an early stage. The sensitivity and specificity of clinical exosome biomarkers need to be enhanced. Knowledge of exosomes is not only important for understanding the significance of cancer progression but also for providing clinicians with useful information for the diagnosis, treatment, and discovery of methods to prevent cancer from recurring. The widespread adoption of diagnostic tools based on exosomes may revolutionize cancer diagnosis and treatment. Tumor metastasis, chemoresistance, and immunity are all aided by exosomes. A potential new approach to cancer therapy involves preventing metastasis by inhibiting miRNA intracellular signaling and blocking the formation of pre-metastatic niches. For colorectal patients, exosomes represent a promising area of investigation for improving the diagnosis, treatment, and management. Reported data demonstrate that the serum expression level of certain exosomal miRNA is significantly higher in primary colorectal cancer patients. The present review discusses mechanisms and clinical implications of exosomes in colorectal cancer.
    Keywords:  cancer; colorectal cancer; exosomal miRNA; exosome; lncRNA
    DOI:  https://doi.org/10.3390/ijms24054382
  2. Cancers (Basel). 2023 Feb 24. pii: 1456. [Epub ahead of print]15(5):
    Extracellular Vesicle-DNA: The Next Liquid Biopsy Biomarker for Early Cancer Diagnosis?
    Irène Tatischeff.
      After a short introduction about the history of liquid biopsy, aimed to noninvasively replace the common tissue biopsy as a help for cancer diagnosis, this review is focused on extracellular vesicles (EVs), as the main third component, which is now coming into the light of liquid biopsy. Cell-derived EV release is a recently discovered general cellular property, and EVs harbor many cellular components reflecting their cell of origin. This is also the case for tumoral cells, and their cargoes might therefore be a "treasure chest" for cancer biomarkers. This has been extensively explored for a decade, but the EV-DNA content escaped this worldwide query until recently. The aim of this review is to gather the pilot studies focused on the DNA content of circulating cell-derived EVs, and the following five years of studies about the circulating tumor EV-DNA. The recent preclinical studies about the circulating tEV-derived gDNA as a potential cancer biomarker developed into a puzzling controversy about the presence of DNA into exosomes, coupled with an increased unexpected non vesicular complexity of the extracellular environment. This is discussed in the present review, together with the challenges that need to be solved before any efficient clinical transfer of EV-DNA as a quite promising cancer diagnosis biomarker.
    Keywords:  EV-associated DNA (EV-DNA); cancer diagnosis; exosomes (EXs); extracellular vesicles (EVs); liquid biopsy (LB)
    DOI:  https://doi.org/10.3390/cancers15051456
  3. Front Pharmacol. 2023 ;14 1093175
    Unraveling the significance of exosomal circRNAs in cancer therapeutic resistance.
    Fanhua Kang, Yuanliang Yan, Yuanhong Liu, Qiuju Liang, Zhijie Xu, Wei Zhu, Abhimanyu Thakur.
      Exosomes are nanoscale extracellular vesicles secreted by a variety of cells, affecting the physiological and pathological homeostasis. They carry various cargoes including proteins, lipids, DNA, and RNA and have emerged as critical mediators of intercellular communication. During cell-cell communication, they can internalize either by autologous or heterologous recipient cells, which activate different signaling pathways, facilitating malignant progression of cancer. Among different types of cargoes in exosomes, the endogenous non-coding RNAs, such as circular RNAs (or circRNAs), have gained tremendous attention for their high stability and concentration, playing promising functional roles in cancer chemotherapeutic response by regulating the targeted gene expression. In this review, we primarily described the emerging evidence demonstrating the important roles of circular RNAs derived from exosomes in the regulation of cancer-associated signaling pathways that were involved in cancer research and therapeutic interventions. Additionally, the relevant profiles of exosomal circRNAs and their biological implications have been discussed, which is under investigation for their potential effect on the control of cancer therapeutic resistance.
    Keywords:  cancer; circular RNAs; drug resistance; exosomes; extracellular vesicles
    DOI:  https://doi.org/10.3389/fphar.2023.1093175
  4. Front Genet. 2023 ;14 1052731
    Exosomal microRNAs in cancer: Potential biomarkers and immunotherapeutic targets for immune checkpoint molecules.
    Faizah Alotaibi.
      Exosomes are small extracellular vesicles with a lipid bilayer structure secreted from different cell types which can be found in various body fluids including blood, pleural fluid, saliva and urine. They carry different biomolecules including proteins, metabolites, and amino acids such as microRNAs which are small non-coding RNAs that regulate gene expression and promote cell-to-cell communication. One main function of the exosomal miRNAs (exomiRs) is their role in cancer pathogenesis. Alternation in exomiRs expression could indicate disease progression and can regulate cancer growth and facilitate drug response/resistance. It can also influence the tumour microenvironment by controlling important signaling that regulating immune checkpoint molecules leading to activation of T cell anti-tumour immunity. Therefore, they can be used as potential novel cancer biomarkers and innovative immunotherapeutic agents. This review highlights the use of exomiRs as potential reliable biomarkers for cancer diagnosis, treatment response and metastasis. Finally, discuses their potential as immunotherapeutic agents to regulate immune checkpoint molecules and promote T cell anti-tumour immunity.
    Keywords:  biomarker; cancer; clinical implication; exosomal miRNA; extracellular vesicles (EVs); immune checkpoint molecules; liquid bioposy; small non-coding RNAs (sncRNAs)
    DOI:  https://doi.org/10.3389/fgene.2023.1052731
  5. Zhonghua Gan Zang Bing Za Zhi. 2022 Nov 20. 30(11): 1248-1252
    [Research progress and clinical application value of exosomal circRNAs in hepatocellular carcinoma].
    C F Li, Y K Liu, Y F Li.
      Primary liver cancer (hereinafter referred to as HCC) is the sixth most common type of cancer and the third leading cause of cancer-related mortality worldwide. Since patients in the early stage of HCC are typically asymptomatic and there are currently no specific detection methods for the early stage of HCC, the majority of patients are diagnosed in the late stage. Exosomes carry proteins, non-coding RNAs, such as cyclic RNAs (circRNAs), and other biological molecules. Patients with hepatocellular carcinoma have a higher concentration of serum exosomes than healthy individuals, and the circRNAs in the exosomes can reflect the source cells and real-time disease status, suggesting it has the potential to detect liver cancer early. This paper focuses on the latest progress of exosomal circRNAs and analyzes the potential value of exosomes in the early diagnosis, treatment, and progression of HCC.
    DOI:  https://doi.org/10.3760/cma.j.cn501113-20211018-00513
  6. Cancer Gene Ther. 2023 Mar 08.
    Loss of exosomal miR-200b-3p from hypoxia cancer-associated fibroblasts promotes tumorigenesis and reduces sensitivity to 5-Flourouracil in colorectal cancer via upregulation of ZEB1 and E2F3.
    Wenjing Gong, Yang Guo, Hang Yuan, Rui Chai, Ziang Wan, Boan Zheng, Xinye Hu, Bingchen Chen, Shan Gao, Qiaoqiong Dai, Peng Yu, Shiliang Tu.
      Hypoxia-mediated tumor progression is a major clinical challenge in human cancers including colorectal cancer (CRC). In addition, exosome-mediated transfer of miRNAs from cancer-associated fibroblasts (CAFs) to cancer cells could promote tumor progression. However, the mechanisms by which hypoxia CAFs promotes CRC progression remain largely unknown. CAFs and normal fibroblasts (NFs) were isolated from CRC tissues and adjacent normal tissues. Next, exosomes were isolated from the supernatant of CAFs that cultured under normoxia (CAFs-N-Exo) and hypoxia (CAFs-H-Exo). RNA-sequencing was then performed to identify differentially expressed miRNAs (DEMs) between CAFs-N-Exo and CAFs-H-Exo. Compared with exosomes derived from normoxia CAFs, exosomes derived from hypoxic CAFs were able to promote CRC cell proliferation, migration, invasion, stemness and reduce the sensitivity of CRC cells to 5-fluorouracil (5-FU). In addition, miR-200b-3p levels were dramatically decreased in exosomes derived from hypoxic CAFs. Remarkably, increasing exosomal miR-200b-3p in hypoxic CAFs reversed the promoting effects of hypoxic CAFs on CRC cell growth in vitro and in vivo. Furthermore, miR-200b-3p agomir could inhibit CRC cell migration, invasion, stemness and increase the sensitivity of SW480 cells to 5-FU via downregulating ZEB1 and E2F3. Collectively, loss of exosomal miR-200b-3p in hypoxia CAFs could contribute to CRC progression via upregulation of ZEB1 and E2F3. Thus, increasing exosomal miR-200b-3p might serve as an alternative approach for the treatment of CRC.
    DOI:  https://doi.org/10.1038/s41417-023-00591-5
  7. Int J Mol Sci. 2023 Feb 27. pii: 4593. [Epub ahead of print]24(5):
    Hepatocellular Carcinoma Cell-Derived Exosomal miR-21-5p Induces Macrophage M2 Polarization by Targeting RhoB.
    Haiyang Yu, Jing Pan, Siyue Zheng, Deyang Cai, Aixiang Luo, Zanxian Xia, Jufang Huang.
      M2-like polarized tumor-associated macrophages (TAMs) are the major component of infiltrating immune cells in hepatocellular carcinoma (HCC), which have been proved to exhibit significant immunosuppressive and pro-tumoral effects. However, the underlying mechanism of the tumor microenvironment (TME) educating TAMs to express M2-like phenotypes is still not fully understood. Here, we report that HCC-derived exosomes are involved in intercellular communications and exhibit a greater capacity to mediate TAMs' phenotypic differentiation. In our study, HCC cell-derived exosomes were collected and used to treat THP-1 cells in vitro. Quantitative polymerase chain reaction (qPCR) results showed that the exosomes significantly promoted THP-1 macrophages to differentiate into M2-like macrophages, which have a high production of transforming growth factor-β (TGF-β) and interleukin (IL)-10. The analysis of bioinformatics indicated that exosomal miR-21-5p is closely related to TAM differentiation and is associated with unfavorable prognosis in HCC. Overexpressing miR-21-5p in human monocyte-derived leukemia (THP-1) cells induced down-regulation of IL-1β levels; however, it enhanced production of IL-10 and promoted the malignant growth of HCC cells in vitro. A reporter assay confirmed that miR-21-5p directly targeted Ras homolog family member B (RhoB) 3'-untranslatedregion (UTR) in THP-1 cells. Downregulated RhoB levels in THP-1 cells would weaken mitogen-activated protein kinase (MAPK) axis signaling pathways. Taken together, tumor-derived miR-21-5p promote the malignant advance of HCC, which mediated intercellular crosstalk between tumor cells and macrophages. Targeting M2-like TAMs and intercepting their associated signaling pathways would provide potentially specific and novel therapeutic approaches for HCC treatment.
    Keywords:  HCC-derived exosomes; RhoB; macrophages; miR-21-5p; polarization
    DOI:  https://doi.org/10.3390/ijms24054593
  8. Front Oncol. 2023 ;13 1056903
    The BAP31/miR-181a-5p/RECK axis promotes angiogenesis in colorectal cancer via fibroblast activation.
    Qi Zhang, Changli Wang, Ruijia Li, Jingjing Liu, Jiyu Wang, Tianyi Wang, Bing Wang.
       Background: B-cell receptor-associated protein 31 (BAP31) has been recognized as a tumor-associated protein and has largely been shown to promote metastasis in a variety of cancers. Cancer metastasis arises through multistep pathways, and the induction of angiogenesis is shown to be a rate-limiting step in the process of tumor metastasis.
    Methods and results: This study explored the effect of BAP31 on colorectal cancer (CRC) angiogenesis by regulating the tumor microenvironment. First, exosomes from BAP31-regulated CRCs affected the transition of normal fibroblasts to proangiogenic cancer-associated fibroblasts (CAFs) in vivo and in vitro. Next, microRNA sequencing was performed to analyze the microRNA expression profile of exosomes secreted from BAP31- overexpressing CRCs. The results indicated that the expression of BAP31 in CRCs significantly altered the levels of exosomal microRNAs, such as miR-181a- 5p. Meanwhile, an in vitro tube formation assay showed that fibroblasts with high levels of miR-181a-5p significantly promoted endothelial cell angiogenesis. Critically, we first identified that miR-181a-5p directly targeted the 3'-untranslated region (3'UTR) of reversion-inducing cysteine-rich protein with kazal motifs (RECK) using the dual-luciferase activity assay, which drove fibroblast transformation into proangiogenic CAFs by upregulating matrix metalloproteinase-9 (MMP-9) and phosphorylation of mothers against decapentaplegic homolog 2/Mothers against decapentaplegic homolog 3 (Smad2/3).
    Conclusion: Exosomes from BAP31-overexpressing/BAP31-knockdown CRCs are found to manipulate the transition of fibroblasts into proangiogenic CAFs by the miR-181a-5p/RECK axis.
    Keywords:  BAP31; angiogenesis; exosomes; fibroblast activation; miR-181a-5p
    DOI:  https://doi.org/10.3389/fonc.2023.1056903
  9. Environ Toxicol. 2023 Mar 07.
    Exosomal ZFPM2-AS1 contributes to tumorigenesis, metastasis, stemness, macrophage polarization, and infiltration in hepatocellular carcinoma through PKM mediated glycolysis.
    Wenjing Ji, Jie Bai, Yue Ke.
       BACKGROUND: With high morbidity and mortality, hepatocellular carcinoma (HCC) deserves further exploration in its pathogenesis mechanisms for promising prognostic and therapeutic markers. This research was conducted to dig out roles of exosomal ZFPM2-AS1 in HCC.
    METHODS: The level of exosomal ZFPM2-AS1 in HCC tissue and cells was determined by Real-time fluorescence quantitative PCR. Pull-down assay and dual-luciferase reporter assay were performed to identify interactions between ZFPM2-AS1 and miRNA-18b-5p, as well as miRNA-18b-5p and PKM. Western blotting was employed to explore the potential regulatory mechanism. Several in vitro assays were conducted in mice xenograft and orthotopic transplantation models to investigate impacts of exosomal ZFPM2-AS1 on HCC development, metastasis, and macrophage infiltration.
    RESULTS: ZFPM2-AS1 was activated in HCC tissue and cells, with high enrichment in HCC-derived exosomes. Exosomal ZFPM2-AS1 enhances the cell abilities and stemness of HCC. MiRNA-18b-5p was directly targeted by ZFPM2-AS1 which triggered PKM expression via sponging miR-18b-5p. Exosomal ZFPM2-AS1 modulated glycolysis via PKM in an HIF-1α dependent way in HCC, promoting M2 polarization, and macrophage recruitment. Furthermore, exosomal ZFPM2-AS1 enhanced HCC cell growth, metastasis, and M2 infiltration in vivo.
    CONCLUSIONS: Exosomal ZFPM2-AS1 exerted regulatory function on the progression of HCC via miR-18b-5p/PKM axis. ZFPM2-AS1 could be promising biomarker for the diagnosis and therapies of HCC.
    Keywords:  exosome; glycolysis; hepatocellular carcinoma; lncRNA; macrophage polarization
    DOI:  https://doi.org/10.1002/tox.23767
  10. Int J Nanomedicine. 2023 ;18 1063-1083
    Long Non-Coding RNAs Within Macrophage-Derived Exosomes Promote BMSC Osteogenesis in a Bone Fracture Rat Model.
    Dong Wang, Yang Liu, Shuo Diao, Lei Shan, Junlin Zhou.
       Purpose: To investigate the effect of macrophage exosomal long non-coding (lnc)RNAs on bone mesenchymal stem cell (BMSC) osteogenesis and the associated mechanism.
    Methods: Rat BMSCs and spleen macrophages were co-cultured with serum derived from the fracture microenvironment of rat tibia. BMSC osteogenesis was evaluated using Alizarin red staining and the expression of BMP-2, RUNX2, OPN, and OC mRNA. BMSC osteogenesis was evaluated after co-culture with macrophages stimulated using hypoxic conditions or colony-stimulating factor (CSF). The uptake of macrophage-derived exosomes by BMSCs was evaluated using the exosome uptake assay. High-throughput sequencing and bioinformatics analyses were performed to identify key lncRNAs in the macrophage exosomes. The effect of lncRNA expression levels on BMSC osteogenesis was also assessed using a lncRNA overexpression plasmid and siRNA technology. M1 and M2 macrophages were distinguished using flow cytometry and the key exosomal lncRNA was detected by in situ hybridization.
    Results: In the fracture microenvironment, macrophages (stimulated using either hypoxia or CSF) significantly increased the osteogenic ability of BMSCs. We showed that BMSCs assimilated macrophage-derived vesicles and that the inhibition of exosomal secretion significantly attenuated the macrophage-mediated induction of BMSC osteogenesis. The hypoxia condition led to the up-regulation of 310 lncRNAs and the down-regulation of 575 lncRNAs in macrophage exosomes, while CSF stimulation caused the up-regulation of 557 lncRNAs and the down-regulation of 407 lncRNAs. In total, 108 lncRNAs were co-up-regulated and 326 lncRNAs were co-down-regulated under both conditions. We eventually identified LOC103691165 as a key lncRNA that promoted BMSC osteogenesis and was expressed at similar levels in both M1 and M2 macrophages.
    Conclusion: In the fracture microenvironment, M1 and M2 macrophages promoted BMSC osteogenesis by secreting exosomes containing LOC103691165.
    Keywords:  BMSCs osteogenesis; LOC103691165; bone fracture microenvironment; lncRNAs; macrophage exosomes
    DOI:  https://doi.org/10.2147/IJN.S398446
  11. Cell Mol Biol Lett. 2023 Mar 05. 28(1): 18
    Exosomal Mir-3613-3p derived from oxygen-glucose deprivation-treated brain microvascular endothelial cell promotes microglial M1 polarization.
    Mengqi Zhang, Qian Wu, Mimi Tang, Zhuohui Chen, Haiyue Wu.
       BACKGROUND: Brain microvascular endothelial cell (BMEC) injury can affect neuronal survival by modulating immune responses through the microenvironment. Exosomes are important vehicles of transport between cells. However, the regulation of the subtypes of microglia by BMECs through the exosome transport of microRNAs (miRNAs) has not been established.
    METHODS: In this study, exosomes from normal and oxygen-glucose deprivation (OGD)-cultured BMECs were collected, and differentially expressed miRNAs were analyzed. BMEC proliferation, migration, and tube formation were analyzed using MTS, transwell, and tube formation assays. M1 and M2 microglia and apoptosis were analyzed using flow cytometry. miRNA expression was analyzed using real-time polymerase chain reaction (RT-qPCR), and IL-1β, iNOS, IL-6, IL-10, and RC3H1 protein concentrations were analyzed using western blotting.
    RESULTS: We found that miR-3613-3p was enriched in BMEC exosome by miRNA GeneChip assay and RT-qPCR analysis. miR-3613-3p knockdown enhanced cell survival, migration, and angiogenesis in the OGD-treated BMECs. In addition, BMECs secrete miR-3613-3p to transfer into microglia via exosomes, and miR-3613-3p binds to the RC3H1 3' untranslated region (UTR) to reduce RC3H1 protein levels in microglia. Exosomal miR-3613-3p promotes microglial M1 polarization by inhibiting RC3H1 protein levels. BMEC exosomal miR-3613-3p reduces neuronal survival by regulating microglial M1 polarization.
    CONCLUSIONS: miR-3613-3p knockdown enhances BMEC functions under OGD conditions. Interfering with miR-3613-3p expression in BMSCs reduced the enrichment of miR-3613-3p in exosomes and enhanced M2 polarization of microglia, which contributed to reduced neuronal apoptosis.
    Keywords:  Brain microvascular endothelial cell; Exosome; Ischemic stroke; Macrophage; Neuron
    DOI:  https://doi.org/10.1186/s11658-023-00432-1
  12. Clin Exp Pharmacol Physiol. 2023 Mar 11.
    Exosomal miR-21-5p derived from multiple myeloma cells promote renal epithelial-mesenchymal transition through targeting TGF-β/SMAD7 signaling pathway.
    Liping Liu, Langni Liu, Rui Liu, Jing Liu, Qian Cheng.
      The prognosis of multiple myeloma (MM) patients combined with renal insufficiency is poor. Renal fibrosis is an important pathological cause for MM patients combined with renal insufficiency. It is reported that epithelial-mesenchymal transition (EMT) of renal proximal tubular epithelial cells is an important mechanism in renal fibrosis. We speculated that EMT might play an important role in the renal insufficiency of MM with unclear mechanism. MM cells derived exosomes could affect the function of targeted cells by delivering miRNAs. Literature showed that the expression of miR-21 is closely related to EMT. In this research, we found that co-culture of HK-2 cells(human renal proximal tubular epithelial cells)and exosomes derived from MM cells promoted the EMT of HK-2 cells, resulting in the down-regulation of epithelial-related marker (E-cadherin)，and up-regulation of stroma-related marker (Vimentin). Meanwhile, the expression of SMAD7, one of the downstream targets in the TGF-β signaling pathway, was suppressed and the expression of TGF-β was increased. After transfecting the inhibitor of miR-21 in MM cells, the expression of miR-21 in exosomes secreted by MM cells was significantly decreased, and the co-culture of these treated exosomes and HK-2 cells inhibited the EMT of HK-2 cells. In conclusion, these findings showed that exosomal miR-21 derived from MM cells could promote renal epithelial-mesenchymal transition through targeting TGF-β/SMAD7 signaling pathway.
    Keywords:  Epithelial-Mesenchymal Transition; Exosomes; MicroRNAs; Multiple myeloma; SMAD7; TGF-β
    DOI:  https://doi.org/10.1111/1440-1681.13768
  13. J Exp Clin Cancer Res. 2023 Mar 10. 42(1): 59
    Exosomal cargos-mediated metabolic reprogramming in tumor microenvironment.
    Shiming Tan, Yiqing Yang, Wenjuan Yang, Yaqian Han, Lisheng Huang, Ruiqian Yang, Zifan Hu, Yi Tao, Lin Liu, Yun Li, Linda Oyang, Jinguan Lin, Qiu Peng, Xianjie Jiang, Xuemeng Xu, Longzheng Xia, Mingjing Peng, Nayiyuan Wu, Yanyan Tang, Deliang Cao, Qianjin Liao, Yujuan Zhou.
      Metabolic reprogramming is one of the hallmarks of cancer. As nutrients are scarce in the tumor microenvironment (TME), tumor cells adopt multiple metabolic adaptations to meet their growth requirements. Metabolic reprogramming is not only present in tumor cells, but exosomal cargos mediates intercellular communication between tumor cells and non-tumor cells in the TME, inducing metabolic remodeling to create an outpost of microvascular enrichment and immune escape. Here, we highlight the composition and characteristics of TME, meanwhile summarize the components of exosomal cargos and their corresponding sorting mode. Functionally, these exosomal cargos-mediated metabolic reprogramming improves the "soil" for tumor growth and metastasis. Moreover, we discuss the abnormal tumor metabolism targeted by exosomal cargos and its potential antitumor therapy. In conclusion, this review updates the current role of exosomal cargos in TME metabolic reprogramming and enriches the future application scenarios of exosomes.
    Keywords:  Adipocytes; Angiogenesis; CAFs; ECM; Exosomal cargo; Metabolism; Stellate cells; T lymphocytes; TAMs; TME
    DOI:  https://doi.org/10.1186/s13046-023-02634-z
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