Effect of hepatocellular carcinoma cell-derived exosomes on M2 polarization of tumor-associated macrophages

Tao YAO; Zhihong XU; Jiyou YAO; Yu XIA; Minqiang LU; Tian LAN; Bing LIU

doi:10.3969/j.issn.1001-5256.2022.03.013

Volume 38 Issue 3

Mar. 2022

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Article Navigation > Journal of Clinical Hepatology > 2022 > 38(3): 558-562

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Effect of hepatocellular carcinoma cell-derived exosomes on M2 polarization of tumor-associated macrophages

DOI: 10.3969/j.issn.1001-5256.2022.03.013

Tao YAO¹,
Zhihong XU¹,
Jiyou YAO²,
Yu XIA²,
Minqiang LU²,
Tian LAN¹,
Bing LIU^{1
,
,
,}

1.
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China
2.
Second Department of Hepatobiliary Surgery, The Second Affiliated Hospital of South China University of Technology & Guangzhou First People's Hospital, Guangzhou 510180, China

Research funding:

Innovation Team of Early Drug Toxicity Evaluation (2018KCXTD016);

Guangzhou Science and Technology Program (202002030387)

More Information

Corresponding author: LIU Bing, liubing52000@163.com(ORCID:0000-0002-3144-5073)
Received Date: 2021-07-14
Accepted Date: 2021-09-10
Published Date: 2022-03-20

Abstract

Abstract

Objective To investigate the effect of exosomes derived from hepatocellular carcinoma cells on the polarization of tumor-associated macrophages (TAMs), and to reveal the novel mechanism of hepatocellular carcinoma formation. Methods Hepatocellular carcinoma cell-derived exosomes were isolated by ultracentrifugation, and the characteristics of exosomes were identified by transmission electron microscope (TEM), Dynamic Light Scattering (DLS), and Western blotting. The model of macrophage polarization was induced and verified by quantitative real-time PCR and Western blotting. The t-test was used for comparison of normally distributed continuous data between two groups. A one-way analysis of variance was used for comparison between multiple groups, and the LSD-t-test was used for further comparison between two groups. Results TEM showed that hepatocellular carcinoma cell-derived exosomes were round or oval vesicles, LDS showed that the exosomes had a particle size of 172.65±2.34 nm, and Western blotting showed highly positive expression of the biomarkers TSG101 and CD63 in exosomes. There was a significant increase in the expression of CD68 after the addition of 15 ng phorbol ester to induce human-derived mononuclear macrophages for 24 hours to achieve adherent growth (1.00±0.25 vs 6.67±0.98, t=11.20, P < 0.001). Western blotting showed that compared with the control group (L02 cell-derived exosomes), the hepatocellular carcinoma cell-derived exosomes (at low, middle, and high doses) induced M2 polarization of macrophages and increased the expression of the markers Arg-1 and CD163 (all P < 0.05). Conclusion Hepatocellular carcinoma cell-derived exosomes promote M2 polarization of TAMs.
- Carcinoma, Hepatocellular,
- Exosomes,
- Macrophages

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[1]	CHEN R, XU X, TAO Y, et al. Exosomes in hepatocellular carcinoma: A new horizon[J]. Cell Commun Signal, 2019, 17(1): 1. DOI: 10.1186/s12964-018-0315-1.
[2]	VILLANUEVA A. Hepatocellular carcinoma[J]. N Engl J Med, 2019, 380(15): 1450-1462. DOI: 10.1056/NEJMra1713263.
[3]	ROCHE B, COILLY A, DUCLOS-VALLEE JC, et al. The impact of treatment of hepatitis C with DAAs on the occurrence of HCC[J]. Liver Int, 2018, 38(Suppl 1): 139-145. DOI: 10.1111/liv.13659.
[4]	WU Y, ZHANG J, ZHANG X, et al. Cancer stem cells: A potential breakthrough in HCC-targeted therapy[J]. Front Pharmacol, 2020, 11: 198. DOI: 10.3389/fphar.2020.00198.
[5]	TACKE F. Targeting hepatic macrophages to treat liver diseases[J]. J Hepatol, 2017, 66(6): 1300-1312. DOI: 10.1016/j.jhep.2017.02.026.
[6]	WU J, GAO W, TANG Q, et al. M2 macrophage-derived exosomes facilitate HCC metastasis by transferring α(M) β(2) integrin to tumor cells[J]. Hepatology, 2021, 73(4): 1365-1380. DOI: 10.1002/hep.31432.
[7]	LI W, NG JM, WONG CC, et al. Molecular alterations of cancer cell and tumour microenvironment in metastatic gastric cancer[J]. Oncogene, 2018, 37(36): 4903-4920. DOI: 10.1038/s41388-018-0341-x.
[8]	NGAMBENJAWONG C, GUSTAFSON HH, PUN SH. Progress in tumor-associated macrophage (TAM)-targeted therapeutics[J]. Adv Drug Deliv Rev, 2017, 114: 206-221. DOI: 10.1016/j.addr.2017.04.010.
[9]	HINSHAW DC, SHEVDE LA. The tumor microenvironment innately modulates cancer progression[J]. Cancer Res, 2019, 79(18): 4557-4566. DOI: 10.1158/0008-5472.CAN-18-3962.
[10]	PEGTEL DM, GOULD SJ. Exosomes[J]. Annu Rev Biochem, 2019, 88: 487-514. DOI: 10.1146/annurev-biochem-013118-111902.
[11]	HARDING C, HEUSER J, STAHL P. Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes[J]. J Cell Biol, 1983, 97(2): 329-339. DOI: 10.1083/jcb.97.2.329.
[12]	PAN BT, JOHNSTONE RM. Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: Selective externalization of the receptor[J]. Cell, 1983, 33(3): 967-978. DOI: 10.1016/0092-8674(83)90040-5.
[13]	PURUSHOTHAMAN A, BANDARI SK, LIU J, et al. Fibronectin on the surface of myeloma cell-derived exosomes mediates exosome-cell interactions[J]. J Biol Chem, 2016, 291(4): 1652-1663. DOI: 10.1074/jbc.M115.686295.
[14]	WANG F, LI L, PIONTEK K, et al. Exosome miR-335 as a novel therapeutic strategy in hepatocellular carcinoma[J]. Hepatology, 2018, 67(3): 940-954. DOI: 10.1002/hep.29586.
[15]	QIAN M, WANG S, GUO X, et al. Hypoxic glioma-derived exosomes deliver microRNA-1246 to induce M2 macrophage polarization by targeting TERF2IP via the STAT3 and NF-κB pathways[J]. Oncogene, 2020, 39(2): 428-442. DOI: 10.1038/s41388-019-0996-y.
[16]	LI QF, XIA T, SHI CW, et al. Effects of exosomes secreted by hepatocellular carcinoma cells under hypoxic environment on homologous cell activity[J]. Chin J Gerontol, 2022, 42(3): 672-675. 李全富, 夏天, 石春薇, 等. 肝癌细胞低氧环境下分泌的外泌体对同源细胞活性的影响[J]. 中国老年学杂志, 2022, 42(3): 672-675.
[17]	ZHAO S, MI Y, GUAN B, et al. Tumor-derived exosomal miR-934 induces macrophage M2 polarization to promote liver metastasis of colorectal cancer[J]. J Hematol Oncol, 2020, 13(1): 156. DOI: 10.1186/s13045-020-00991-2.
[18]	FANG T, LV H, LV G, et al. Tumor-derived exosomal miR-1247-3p induces cancer-associated fibroblast activation to foster lung metastasis of liver cancer[J]. Nat Commun, 2018, 9(1): 191. DOI: 10.1038/s41467-017-02583-0.
[19]	LOU G, CHEN Z, ZHENG M, et al. Mesenchymal stem cell-derived exosomes as a new therapeutic strategy for liver diseases[J]. Exp Mol Med, 2017, 49(6): e346. DOI: 10.1038/emm.2017.63.
[20]	GANDHAM S, SU X, WOOD J, et al. Technologies and standardization in research on extracellular vesicles[J]. Trends Biotechnol, 2020, 38(10): 1066-1098. DOI: 10.1016/j.tibtech.2020.05.012.
[21]	TI D, HAO H, TONG C, et al. LPS-preconditioned mesenchymal stromal cells modify macrophage polarization for resolution of chronic inflammation via exosome-shuttled let-7b[J]. J Transl Med, 2015, 13: 308. DOI: 10.1186/s12967-015-0642-6.

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Effect of hepatocellular carcinoma cell-derived exosomes on M2 polarization of tumor-associated macrophages

DOI: 10.3969/j.issn.1001-5256.2022.03.013

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Effect of hepatocellular carcinoma cell-derived exosomes on M2 polarization of tumor-associated macrophages

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