Current status of research on exosomes in malignancies

doi:10.3760/cma.j.cn371439-20230315-00092

Abstract

Abstract:

Exosomes are membranous vesicles secreted by most eukaryotic cells， which are approximately 30-150 nm in diameter and contain RNA， proteins and lipids closely related to their function and origin， playing an important role in cell-to-cell communication. It can promote tumor progression by promoting the proliferation and migration of tumor cells， improving the tumor microenvironment and inhibiting the immune response. In addition， exosomes are expressed at high levels in certain tumors and can be used as predictors of cancer for early diagnosis. It can also be used as a carrier to carry targeted drugs to the local tumor to exert an inhibitory effect.

Key words: Exosomes, Neoplasms, Proliferation, Migration, Immunity, Angiogenesis

Zhang Yuan, Bai Zhiyu, Li Qi, Feng Qinmei. Current status of research on exosomes in malignancies[J]. Journal of International Oncology, 2023, 50(8): 484-488.

References 52

[1]	Pan BT, Teng K, Wu C, et al. Electron microscopic evidence for externalization of the transferrin receptor in vesicular form in sheep reticulocytes[J]. J Cell Biol, 1985, 101(3): 942-948. DOI: 10.1083/jcb.101.3.942. pmid: 2993317
[2]	Zhu L, Sun HT, Wang S, et al. Isolation and characterization of exosomes for cancer research[J]. J Hematol Oncol, 2020, 13(1): 152. DOI: 10.1186/s13045-020-00987-y.
[3]	Dai J, Su Y, Zhong S, et al. Exosomes: key players in cancer and potential therapeutic strategy[J]. Signal Transduct Target Ther, 2020, 5(1): 145. DOI: 10.1038/s41392-020-00261-0.
[4]	Zhang L, Yu D. Exosomes in cancer development, metastasis, and immunity[J]. Biochim Biophys Acta Rev Cancer, 2019, 1871(2): 455-468. DOI: 10.1016/j.bbcan.2019.04.004.
[5]	Wee I, Syn N, Sethi G, et al. Role of tumor-derived exosomes in cancer metastasis[J]. Biochim Biophys Acta Rev Cancer, 2019, 1871(1): 12-19. DOI: 10.1016/j.bbcan.2018.10.004.
[6]	Gangoda L, Liem M, Ang CS, et al. Proteomic profiling of exosomes secreted by breast cancer cells with varying metastatic potential[J]. Proteomics, 2017, 17(23/24): 1600370. DOI: 10.1002/pmic.201600370.
[7]	Li Z, Yanfang W, Li J, et al. Tumor-released exosomal circular RNA PDE8A promotes invasive growth via the miR-338/MACC1/Met pathway in pancreatic cancer[J]. Cancer Lett, 2018, 432: 237-250. DOI: 10.1016/j.canlet.2018.04.035. pmid: 29709702
[8]	Zhang W, Zheng X, Yu Y, et al. Renal cell carcinoma-derived exosomes deliver lncARSR to induce macrophage polarization and promote tumor progression via STAT3 pathway[J]. Int J Biol Sci, 2022, 18(8): 3209-3222. DOI: 10.7150/ijbs.70289. pmid: 35637970
[9]	Fu Q, Zhang Q, Lou Y, et al. Primary tumor-derived exosomes facilitate metastasis by regulating adhesion of circulating tumor cells via SMAD3 in liver cancer[J]. Oncogene, 2018, 37(47): 6105-6118. DOI: 10.1038/s41388-018-0391-0. pmid: 29991801
[10]	黎娜, 罗丽, 杨雅婷, 等. 胶质母细胞瘤外泌体的作用机制研究进展[J]. 生物工程学报, 2023, 39(04):1477-1501. DOI: 10.13345/j.cjb.220777.
[11]	Quezada C, Torres Á, Niechi I, et al. Role of extracellular vesicles in glioma progression[J]. Mol Aspects Med, 2018, 60: 38-51. DOI: 10.1016/j.mam.2017.12.003. pmid: 29222067
[12]	Nieland L, Morsett LM, Broekman MLD, et al. Extracellular vesicle-mediated bilateral communication between glioblastoma and astrocytes[J]. Trends Neurosci, 2021, 44(3): 215-226. DOI: 10.1016/j.tins.2020.10.014. pmid: 33234347
[13]	Abels ER, Maas SLN, Nieland L, et al. Glioblastoma-associated microglia reprogramming is mediated by functional transfer of extracellular miR-21[J]. Cell Rep, 2019, 28(12): 3105-3119.e7. DOI: 10.1016/j.celrep.2019.08.036. pmid: 31533034
[14]	Cai Q, Zhu A, Gong L. Exosomes of glioma cells deliver miR-148a to promote proliferation and metastasis of glioblastoma via targeting CADM1[J]. Bull Cancer, 2018, 105(7/8): 643-651. DOI: 10.1016/j.bulcan.2018.05.003.
[15]	Yang F, Ning Z, Ma L, et al. Exosomal miRNAs and miRNA dysregulation in cancer-associated fibroblasts[J]. Mol Cancer, 2017, 16(1): 148. DOI: 10.1186/s12943-017-0718-4. pmid: 28851377
[16]	Thuringer D, Chanteloup G, Boucher J, et al. Modulation of the inwardly rectifying potassium channel Kir4.1 by the pro-invasive miR-5096 in glioblastoma cells[J]. Oncotarget, 2017, 8(23): 37681-37693. DOI: 10.18632/oncotarget.16949. pmid: 28445150
[17]	Wang S, Jiang G, Wang S,. Neuroprotective role of vniRNA-9 in neurological diseases: a mini review[J/OL]. Curr Mol Med. [2022-10-25][2023-03-13]. https://pubmed.ncbi.nlm.nih.gov/36284391/. DOI: 10.2174/1566524023666221025123132.
[18]	Wang X, Cao Q, Shi Y, et al. Identification of low-dose radiation-induced exosomal circ-METRN and miR-4709-3p/GRB14/PDGFRα pathway as a key regulatory mechanism in glioblastoma progression and radioresistance: functional validation and clinical theranostic significance[J]. Int J Biol Sci, 2021, 17(4): 1061-1078. DOI: 10.7150/ijbs.57168. pmid: 33867829
[19]	Monfared H, Jahangard Y, Nikkhah M, et al. Potential therapeutic effects of exosomes packed with a miR-21-sponge construct in a rat model of glioblastoma[J]. Front Oncol, 2019, 9: 782. DOI: 10.3389/fonc.2019.00782. pmid: 31482067
[20]	Xue P, Huang S, Han X, et al. Exosomal miR-101-3p and miR-423-5p inhibit medulloblastoma tumorigenesis through targeting FOXP4 and EZH2[J]. Cell Death Differ, 2022, 29(1): 82-95. DOI: 10.1038/s41418-021-00838-4.
[21]	Park J, Cho M, Cho J, et al. MicroRNA-101-3p suppresses cancer cell growth by inhibiting the USP47-induced deubiquitination of RPL11[J]. Cancers (Basel), 2022, 14(4): 964. DOI: 10.3390/cancers14040964.
[22]	Kok VC, Yu CC. Cancer-derived exosomes: their role in cancer biology and biomarker development[J]. Int J Nanomedicine, 2020, 15: 8019-8036. DOI: 10.2147/IJN.S272378.
[23]	Lan J, Sun L, Xu F, et al. M2 macrophage-derived exosomes promote cell migration and invasion in colon cancer[J]. Cancer Res, 2019, 79(1): 146-158. DOI: 10.1158/0008-5472.CAN-18-0014. pmid: 30401711
[24]	Liu G, Ouyang X, Sun Y, et al. The miR-92a-2-5p in exosomes from macrophages increases liver cancer cells invasion via altering the AR/PHLPP/p-AKT/β-catenin signaling[J]. Cell Death Differ, 2020, 27(12): 3258-3272. DOI: 10.1038/s41418-020-0575-3.
[25]	VanderVorst K, Dreyer CA, Konopelski SE, et al. Wnt/PCP signa-ling contribution to carcinoma collective cell migration and metastasis[J]. Cancer Res, 2019, 79(8): 1719-1729. DOI: 10.1158/0008-5472.CAN-18-2757. pmid: 30952630
[26]	Zhang H, Deng T, Liu R, et al. Exosome-delivered EGFR regulates liver microenvironment to promote gastric cancer liver metastasis[J]. Nat Commun, 2017, 8: 15016. DOI: 10.1038/ncomms15016. pmid: 28393839
[27]	Lakshmi S, Hughes TA, Priya S. Exosomes and exosomal RNAs in breast cancer: a status update[J]. Eur J Cancer, 2021, 144: 252-268. DOI: 10.1016/j.ejca.2020.11.033. pmid: 33373870
[28]	Hoshino A, Costa-Silva B, Shen TL, et al. Tumour exosome inte-grins determine organotropic metastasis[J]. Nature, 2015, 527(7578): 329-335. DOI: 10.1038/nature15756.
[29]	Sun H, Meng Q, Shi C, et al. Hypoxia-inducible exosomes facilitate liver-tropic premetastatic niche in colorectal cancer[J]. Hepatology, 2021, 74(5): 2633-2651. DOI: 10.1002/hep.32009.
[30]	Chen HL, Li JJ, Jiang F, et al. MicroRNA-4461 derived from bone marrow mesenchymal stem cell exosomes inhibits tumorigenesis by downregulating COPB2 expression in colorectal cancer[J]. Biosci Biotechnol Biochem, 2020, 84(2): 338-346. DOI: 10.1080/09168451.2019.1677452.
[31]	杜坤, 汪兵, 杨盛荣, 等. 骨髓间充质干细胞外泌体miR-126-3p靶向CCR1抑制非小细胞肺癌细胞恶性增殖及转移[J]. 西安交通大学学报(医学版), 2023, 44(2): 189-194. DOI: 10.7652/jdyxb202302006.
[32]	Shimizu A, Sawada K, Kimura T. Pathophysiological role and potential therapeutic exploitation of exosomes in ovarian cancer[J]. Cells, 2020, 9(4): 814. DOI: 10.3390/cells9040814.
[33]	Shao Y, Chen T, Zheng X, et al. Colorectal cancer-derived small extracellular vesicles establish an inflammatory premetastatic niche in liver metastasis[J]. Carcinogenesis, 2018, 39(11): 1368-1379. DOI: 10.1093/carcin/bgy115. pmid: 30184100
[34]	Chen L, Huang H, Zhang W, et al. Exosomes derived from T regulatory cells suppress CD8⁺ cytotoxic T lymphocyte proliferation and prolong liver allograft survival[J]. Med Sci Monit, 2019, 25: 4877-4884. DOI: 10.12659/MSM.917058.
[35]	Hui E, Cheung J, Zhu J, et al. T cell costimulatory receptor CD28 is a primary target for PD-1-mediated inhibition[J]. Science, 2017, 355(6332): 1428-1433. DOI: 10.1126/science.aaf1292. pmid: 28280247
[36]	Zhou Y, Zhang Y, Gong H, et al. The role of exosomes and their applications in cancer[J]. Int J Mol Sci, 2021, 22(22): 12204. DOI: 10.3390/ijms222212204.
[37]	Mao Y, Wang Y, Dong L, et al. Circulating exosomes from esophageal squamous cell carcinoma mediate the generation of B10 and PD-1^high Breg cells[J]. Cancer Sci, 2019, 110(9): 2700-2710. DOI: 10.1111/cas.14122.
[38]	Zhou W, Zhou Y, Chen X, et al. Pancreatic cancer-targeting exosomes for enhancing immunotherapy and reprogramming tumor microenvironment[J]. 2021, 268: 120546. DOI: 10.1016/j.biomaterials.2020.120546.
[39]	Ye L, Zhang Q, Cheng Y, et al. Tumor-derived exosomal HMGB1 fosters hepatocellular carcinoma immune evasion by promoting TIM-1⁺ regulatory B cell expansion[J]. J Immunother Cancer, 2018, 6(1): 145. DOI: 10.1186/s40425-018-0451-6.
[40]	Lv LH, Wan YL, Lin Y, et al. Anticancer drugs cause release of exosomes with heat shock proteins from human hepatocellular carcinoma cells that elicit effective natural killer cell antitumor responses in vitro[J]. J Biol Chem, 2012, 287(19): 15874-15885. DOI: 10.1074/jbc.M112.340588. pmid: 22396543
[41]	Li D, Wang Y, Jin X, et al. NK cell-derived exosomes carry miR-207 and alleviate depression-like symptoms in mice[J]. J Neuroinflammation, 2020, 17(1): 126. DOI: 10.1186/s12974-020-01787-4.
[42]	Egorova A, Shubina A, Sokolov D, et al. CXCR4-targeted modular peptide carriers for efficient anti-VEGF siRNA delivery[J]. Int J Pharm, 2016, 515(1/2): 431-440. DOI: 10.1016/j.ijpharm.2016.10.049.
[43]	Du J, Liang Y, Li J, et al. Gastric cancer cell-derived exosomal microRNA-23a promotes angiogenesis by targeting PTEN[J]. Front Oncol, 2022, 10: 326. DOI: 10.3389/fonc.2020.00326.
[44]	Chen Z, Xie Y, Chen W, et al. MicroRNA-6785-5p-loaded human umbilical cord mesenchymal stem cells-derived exosomes suppress angiogenesis and metastasis in gastric cancer via INHBA[J]. Life Sci, 2021, 284: 119222. DOI: 10.1016/j.lfs.2021.119222.
[45]	Ling X, Zhang G, Xia Y, et al. Exosomes from human urine-derived stem cells enhanced neurogenesis via miR-26a/HDAC6 axis after ischaemic stroke[J]. J Cell Mol Med, 2020, 24(1): 640-654. DOI: 10.1111/jcmm.14774. pmid: 31667951
[46]	Elsharkawi F, Elsabah M, Shabayek M, et al. Urine and serum exosomes as novel biomarkers in detection of bladder cancer[J]. Asian Pac J Cancer Prev, 2019, 20(7): 2219-2224. DOI: 10.31557/APJCP.2019.20.7.2219.
[47]	van der Watt PJ, Okpara MO, Wishart A, et al. Nuclear transport proteins are secreted by cancer cells and identified as potential novel cancer biomarkers[J]. Int J Cancer, 2022, 150(2): 347-361. DOI: 10.1002/ijc.33832.
[48]	Zheng M, Hou L, Ma Y, et al. Exosomal let-7d-3p and miR-30d-5p as diagnostic biomarkers for non-invasive screening of cervical cancer and its precursors[J]. Mol Cancer, 2019, 18(1): 76. DOI: 10.1186/s12943-019-0999-x. pmid: 30940131
[49]	Luo X, Wei J, Yang FL, et al. Exosomal lncRNA HNF1A-AS1 affects cisplatin resistance in cervical cancer cells through regulating microRNA-34b/TUFT1 axis[J]. Cancer Cell Int, 2019, 19: 323. DOI: 10.1186/s12935-019-1042-4. pmid: 31827397
[50]	Zhai LY, Li MX, Pan WL, et al. In situ detection of plasma exosomal microRNA-1246 for breast cancer diagnostics by a Au nanoflare probe[J]. ACS Appl Mater Interfaces, 2018, 10(46): 39478-39486. DOI: 10.1021/acsami.8b12725.
[51]	Santos JC, Lima NDS, Sarian LO, et al. Exosome-mediated breast cancer chemoresistance via miR-155 transfer[J]. Sci Rep, 2018, 8(1): 829. DOI: 10.1038/s41598-018-19339-5. pmid: 29339789
[52]	Raimondi L, De Luca A, Gallo A, et al. Osteosarcoma cell-derived exosomes affect tumor microenvironment by specific packaging of microRNAs[J]. Carcinogenesis, 2020, 41(5): 666-677. DOI: 10.1093/carcin/bgz130. pmid: 31294446