中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R

留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

肝巨噬细胞调控肝癌癌前病变恶变的研究进展

闫瑞娟 焦俊喆 黄玉 闫曙光 魏海梁 常占杰 郭英君 李京涛

引用本文:
Citation:

肝巨噬细胞调控肝癌癌前病变恶变的研究进展

DOI: 10.12449/JCH240527
基金项目: 

国家自然科学基金 (82174330);

陕西省科技厅科研基金 (2022JQ-965);

陕西省科技厅科研基金 (2020ZDLSF05-15);

陕西省科技厅创新团队 (2022TD-55);

陕西省中管局创新团队 (2022-SLRH-LJ-002);

咸阳市科技局科研基金 (L2022ZDYFSF007);

宁夏自然科学基金 (2023AAC03510);

陕西中医药大学学科创新团队建设项目 (2019-YL05)

利益冲突声明:本文不存在任何利益冲突。
作者贡献声明:闫瑞娟负责构思文章思路,设计文章结构并撰写文章;焦俊喆、黄玉、魏海梁负责研究文献,更新、补充相关内容;闫曙光负责设计并讨论文章构架;常占杰负责基础理论指导;郭英君负责修改文章,设计文章结构并参与部分文章撰写;李京涛负责审核文章思路并修改。
详细信息
    通信作者:

    郭英君, 510410652@qq.com (ORCID: 0009-0007-9766-5955)

    李京涛, lijingtao555@163.com (ORCID: 0000-0003-0417-9821)

Research advances in liver macrophages regulating malignant transformation of hepatic precancerous lesions

Research funding: 

National Natural Science Foundation of China (82174330);

Science and Technology Department of Shaanxi Research Fund (2022JQ-965);

Science and Technology Department of Shaanxi Research Fund (2020ZDLSF05-15);

Innovation Team of Science and Technology Department of Shaanxi Province (2022TD-55);

Innovation Team of TCM Administration of Shaanxi Province (2022-SLRH-LJ-002);

Science and Technology Administration of Xianyang City Scientific Research Fund (L2022ZDYFSF007);

Natural Science Foundation of Ningxia (2023AAC03510);

Discipline Innovation Team Building Project of Shaanxi University of Chinese Medicine (2019-YL05)

More Information
  • 摘要: 肝巨噬细胞是肝脏中重要的免疫细胞,其通过极化为M1型和M2型,分别表达“促炎因子”和“抑炎因子”,进而发挥调控炎症损伤反应的作用。肝祖细胞恶变是肝癌癌前病变恶性进展的核心机制,其发生的关键因素是炎症损伤微环境的持续刺激,与M1/M2巨噬细胞极化密切相关。本综述主要围绕“巨噬细胞极化-慢性炎症-肝祖细胞恶变”关系进行探讨,为肝癌癌前病变的预防和治疗提供重要的理论依据。

     

  • 图  1  肝巨噬细胞极化平衡调控肝癌癌前病变恶变示意图

    注: LPS,脂多糖;iNOS,一氧化氮合成酶;MCP-1,单核细胞趋化蛋白-1;CCL2,趋化因子配体2;PDGF,血小板衍生生长因子;Arg1,精氨酸酶1;CD206,甘露糖受体。

    Figure  1.  Schematic diagram of liver macrophage polarization balance regulating malignant transformation of hepatic precancerous lesion

    图  2  肝巨噬细胞极化调控肝祖细胞恶变示意图

    Figure  2.  Schematic diagram of hepatic macrophage polarization regulating malignant degeneration of hepatic progenitor cells

  • [1] VOGEL A, MEYER T, SAPISOCHIN G, et al. Hepatocellular carcinoma[J]. Lancet, 2022, 400( 10360): 1345- 1362. DOI: 10.1016/S0140-6736(22)01200-4.
    [2] WANG C, VEGNA S, JIN HJ, et al. Inducing and exploiting vulnerabilities for the treatment of liver cancer[J]. Nature, 2019, 574( 7777): 268- 272. DOI: 10.1038/s41586-019-1607-3.
    [3] RENZULLI M, BISELLI M, BROCCHI S, et al. New hallmark of hepatocellular carcinoma, early hepatocellular carcinoma and high-grade dysplastic nodules on Gd-EOB-DTPA MRI in patients with cirrhosis: A new diagnostic algorithm[J]. Gut, 2018, 67( 9): 1674- 1682. DOI: 10.1136/gutjnl-2017-315384.
    [4] JIAO JZ, LI JT, YAN SG, et al. Current research status of precancerous dysplastic nodules in hepatocellular carcinoma[J]. J Clin Hepatol, 2017, 33( 5): 974- 978. DOI: 10.3969/j.issn.1001-5256.2017.05.039.

    焦俊喆, 李京涛, 闫曙光, 等. 肝细胞癌癌前异型增生结节的研究现状[J]. 临床肝胆病杂志, 2017, 33( 5): 974- 978. DOI: 10.3969/j.issn.1001-5256.2017.05.039.
    [5] Professional Committee for Prevention and Control of Hepatobiliary and Pancreatic Diseases of Chinese Preventive Medicine Association; Professional Committee for Hepatology, Chinese Research Hospital Association; Chinese Society of Hepatology, Chinese Medical Association, et al. Guideline for stratified screening and surveillance of primary liver cancer(2020 edition)[J]. J Clin Hepatol, 2021, 37( 2): 286- 295. DOI: 10.3969/j.issn.1001-5256.2021.02.009.

    中华预防医学会肝胆胰疾病预防与控制专业委员会, 中国研究型医院学会肝病专业委员会, 中华医学会肝病学分会, 等. 原发性肝癌的分层筛查与监测指南(2020版)[J]. 临床肝胆病杂志, 2021, 37( 2): 286- 295. DOI: 10.3969/j.issn.1001-5256.2021.02.009.
    [6] MARQUARDT JU, ANDERSEN JB, THORGEIRSSON SS. Functional and genetic deconstruction of the cellular origin in liver cancer[J]. Nat Rev Cancer, 2015, 15( 11): 653- 667. DOI: 10.1038/nrc4017.
    [7] ZHU LQ, FINKELSTEIN D, GAO CL, et al. Multi-organ mapping of cancer risk[J]. Cell, 2016, 166( 5): 1132- 1146. DOI: 10.1016/j.cell.2016.07.045.
    [8] MIYAJIMA A, TANAKA M, ITOH T. Stem/progenitor cells in liver development, homeostasis, regeneration, and reprogramming[J]. Cell Stem Cell, 2014, 14( 5): 561- 574. DOI: 10.1016/j.stem.2014.04.010.
    [9] BRIA A, MARDA J, ZHOU JM, et al. Hepatic progenitor cell activation in liver repair[J]. Liver Res, 2017, 1( 2): 81- 87. DOI: 10.1016/j.livres.2017.08.002.
    [10] WU CC, LIN CJ, KUO KK, et al. Correlation between cancer stem cells, inflammation and malignant transformation in a DEN-induced model of hepatic carcinogenesis[J]. Curr Issues Mol Biol, 2022, 44( 7): 2879- 2886. DOI: 10.3390/cimb44070198.
    [11] PU WJ, ZHU H, ZHANG MJ, et al. Bipotent transitional liver progenitor cells contribute to liver regeneration[J]. Nat Genet, 2023, 55( 4): 651- 664. DOI: 10.1038/s41588-023-01335-9.
    [12] LIU WT, GAO L, HOU XJ, et al. TWEAK signaling-induced ID1 expression drives malignant transformation of hepatic progenitor cells during hepatocarcinogenesis[J]. Adv Sci, 2023, 10( 18): e2300350. DOI: 10.1002/advs.202300350.
    [13] NIO K, YAMASHITA T, KANEKO S. The evolving concept of liver cancer stem cells[J]. Mol Cancer, 2017, 16( 1): 4. DOI: 10.1186/s12943-016-0572-9.
    [14] THAN NN, NEWSOME PN. Stem cells for liver regeneration[J]. QJM, 2014, 107( 6): 417- 421. DOI: 10.1093/qjmed/hcu013.
    [15] YAN ZJ, CHEN L, WANG HY. To be or not to be: The double-edged sword roles of liver progenitor cells[J]. Biochim Biophys Acta Rev Cancer, 2023, 1878( 3): 188870. DOI: 10.1016/j.bbcan.2023.188870.
    [16] SIA D, VILLANUEVA A, FRIEDMAN SL, et al. Liver cancer cell of origin, molecular class, and effects onPatient prognosis[J]. Gastroenterology, 2017, 152( 4): 745- 761. DOI: 10.1053/j.gastro.2016.11.048.
    [17] HAIDERI SS, MCKINNON AC, TAYLOR AH, et al. Injection of embryonic stem cell derived macrophages ameliorates fibrosis in a murine model of liver injury[J]. NPJ Regen Med, 2017, 2: 14. DOI: 10.1038/s41536-017-0017-0.
    [18] ZENG JX, JING YY, WU QL, et al. Autophagy is required for hepatic differentiation of hepatic progenitor cells via Wnt signaling pathway[J]. Biomed Res Int, 2021, 2021: 6627506. DOI: 10.1155/2021/6627506.
    [19] NATI M, CHUNG KJ, CHAVAKIS T. The role of innate immune cells in nonalcoholic fatty liver disease[J]. J Innate Immun, 2022, 14( 1): 31- 41. DOI: 10.1159/000518407.
    [20] KHURANA A, NAVIK U, ALLAWADHI P, et al. Spotlight on liver macrophages for halting liver disease progression and injury[J]. Expert Opin Ther Targets, 2022, 26( 8): 707- 719. DOI: 10.1080/14728222.2022.2133699.
    [21] SOUCIE EL, WENG ZM, GEIRSDÓTTIR L, et al. Lineage-specific enhancers activate self-renewal genes in macrophages and embryonic stem cells[J]. Science, 2016, 351( 6274): aad5510. DOI: 10.1126/science.aad5510.
    [22] BLÉRIOT C, DUPUIS T, JOUVION G, et al. Liver-resident macrophage necroptosis orchestrates type 1 microbicidal inflammation and type-2-mediated tissue repair during bacterial infection[J]. Immunity, 2015, 42( 1): 145- 158. DOI: 10.1016/j.immuni.2014.12.020.
    [23] VANNELLA KM, WYNN TA. Mechanisms of organ injury and repair by macrophages[J]. Annu Rev Physiol, 2017, 79: 593- 617. DOI: 10.1146/annurev-physiol-022516-034356.
    [24] LUO Y, XIAO JH. Inflammatory auxo-action in the stem cell division theory of cancer[J]. PeerJ, 2023, 11: e15444. DOI: 10.7717/peerj.15444.
    [25] LI XF, CHEN C, XIANG DM, et al. Chronic inflammation-elicited liver progenitor cell conversion to liver cancer stem cell with clinical significance[J]. Hepatology, 2017, 66( 6): 1934- 1951. DOI: 10.1002/hep.29372.
    [26] SICA A, INVERNIZZI P, MANTOVANI A. Macrophage plasticity and polarization in liver homeostasis and pathology[J]. Hepatology, 2014, 59( 5): 2034- 2042. DOI: 10.1002/hep.26754.
    [27] MURRAY PJ, ALLEN JE, BISWAS SK, et al. Macrophage activation and polarization: Nomenclature and experimental guidelines[J]. Immunity, 2014, 41( 1): 14- 20. DOI: 10.1016/j.immuni.2014.06.008.
    [28] SHAPOURI-MOGHADDAM A, MOHAMMADIAN S, VAZINI H, et al. Macrophage plasticity, polarization, and function in health and disease[J]. J Cell Physiol, 2018, 233( 9): 6425- 6440. DOI: 10.1002/jcp.26429.
    [29] JIN K, LI T, SÁNCHEZ-DUFFHUES G, et al. Involvement of inflammation and its related microRNAs in hepatocellular carcinoma[J]. Oncotarget, 2017, 8( 13): 22145- 22165. DOI: 10.18632/oncotarget.13530.
    [30] YANG L, ZHANG Y. Tumor-associated macrophages: From basic research to clinical application[J]. J Hematol Oncol, 2017, 10( 1): 58. DOI: 10.1186/s13045-017-0430-2.
    [31] MAO YL, WANG BK, XU X, et al. Glycyrrhizic acid promotes M1 macrophage polarization in murine bone marrow-derived macrophages associated with the activation of JNK and NF-κB[J]. Mediators Inflamm, 2015, 2015: 372931. DOI: 10.1155/2015/372931.
    [32] TANG Y, KITISIN K, JOGUNOORI W, et al. Progenitor/stem cells give rise to liver cancer due to aberrant TGF-beta and IL-6 signaling[J]. Proc Natl Acad Sci U S A, 2008, 105( 7): 2445- 2450. DOI: 10.1073/pnas.0705395105.
    [33] HAN CY, YANG Y, SHENG YJ, et al. The mechanism of lncRNA-CRNDE in regulating tumour-associated macrophage M2 polarization and promoting tumour angiogenesis[J]. J Cellular Molecular Medi, 2021, 25( 9): 4235- 4247. DOI: 10.1111/jcmm.16477.
    [34] GUNASSEKARAN GR, POONGKAVITHAI VADEVOO SM, BAEK MC, et al. M1 macrophage exosomes engineered to foster M1 polarization and target the IL-4 receptor inhibit tumor growth by reprogramming tumor-associated macrophages into M1-like macrophages[J]. Biomaterials, 2021, 278: 121137. DOI: 10.1016/j.biomaterials.2021.121137.
    [35] ORECCHIONI M, GHOSHEH Y, PRAMOD AB, et al. Macrophage polarization: Different gene signatures in M1(LPS+) vs. classically and M2(LPS-) vs. alternatively activated macrophages[J]. Front Immunol, 2019, 10: 1084. DOI: 10.3389/fimmu.2019.01084.
    [36] RINGELHAN M, PFISTER D, O’CONNOR T, et al. The immunology of hepatocellular carcinoma[J]. Nat Immunol, 2018, 19( 3): 222- 232. DOI: 10.1038/s41590-018-0044-z.
    [37] Bureau of Medical Administration, National Health Commission of the People’s Republic of China. Guidelines for diagnosis and treatment of primary liver cancer in China(2019 edition)[J]. J Clin Hepatol, 2020, 36( 2): 277- 292. DOI: 10.3969/j.issn.1001-5256.2020.02.007.

    中华人民共和国国家卫生健康委员会医政医管局. 原发性肝癌诊疗规范(2019年版)[J]. 临床肝胆病杂志, 2020, 36( 2): 277- 292. DOI: 10.3969/j.issn.1001-5256.2020.02.007.
    [38] CHEN JM, CHEN L, ZERN MA, et al. The diversity and plasticity of adult hepatic progenitor cells and their niche[J]. Liver Int, 2017, 37( 9): 1260- 1271. DOI: 10.1111/liv.13377.
    [39] HOU XJ, YE F, LI XY, et al. Immune response involved in liver damage and the activation of hepatic progenitor cells during liver tumorigenesis[J]. Cell Immunol, 2018, 326: 52- 59. DOI: 10.1016/j.cellimm.2017.08.004.
    [40] KAUR S, SIDDIQUI H, BHAT MH. Hepatic progenitor cells in action: Liver regeneration or fibrosis?[J]. Am J Pathol, 2015, 185( 9): 2342- 2350. DOI: 10.1016/j.ajpath.2015.06.004.
    [41] ALEKSANDROVA K, BOEING H, NÖTHLINGS U, et al. Inflammatory and metabolic biomarkers and risk of liver and biliary tract cancer[J]. Hepatology, 2014, 60( 3): 858- 871. DOI: 10.1002/hep.27016.
    [42] YANG X, SHAO CC, DUAN LX, et al. Oncostatin M promotes hepatic progenitor cell activation and hepatocarcinogenesis via macrophage-derived tumor necrosis factor-Α[J]. Cancer Lett, 2021, 517: 46- 54. DOI: 10.1016/j.canlet.2021.05.039.
    [43] LI L, CUI L, LIN P, et al. Kupffer-cell-derived IL-6 is repurposed for hepatocyte dedifferentiation via activating progenitor genes from injury-specific enhancers[J]. Cell Stem Cell, 2023, 30( 3): 283- 299. e 9. DOI: 10.1016/j.stem.2023.01.009.
    [44] GALDIERO MR, BONAVITA E, BARAJON I, et al. Tumor associated macrophages and neutrophils in cancer[J]. Immunobiology, 2013, 218( 11): 1402- 1410. DOI: 10.1016/j.imbio.2013.06.003.
    [45] GOSWAMI KK, GHOSH T, GHOSH S, et al. Tumor promoting role of anti-tumor macrophages in tumor microenvironment[J]. Cell Immunol, 2017, 316: 1- 10. DOI: 10.1016/j.cellimm.2017.04.005.
    [46] van HUL N, LANTHIER N, ESPAÑOL SUÑER R, et al. Kupffer cells influence parenchymal invasion and phenotypic orientation, but not the proliferation, of liver progenitor cells in a murine model of liver injury[J]. Am J Pathol, 2011, 179( 4): 1839- 1850. DOI: 10.1016/j.ajpath.2011.06.042.
  • 加载中
图(2)
计量
  • 文章访问数:  160
  • HTML全文浏览量:  96
  • PDF下载量:  24
  • 被引次数: 0
出版历程
  • 收稿日期:  2023-08-15
  • 录用日期:  2023-09-12
  • 出版日期:  2024-05-25
  • 分享
  • 用微信扫码二维码

    分享至好友和朋友圈

目录

    /

    返回文章
    返回