HMGB1/TREM1 crosstalk between heat-injured hepatocytes and macrophages promotes HCC progression after RFA.
Animals
Mice
Liver Neoplasms
/ metabolism
Hepatocytes
/ metabolism
Carcinoma, Hepatocellular
/ metabolism
HMGB1 Protein
/ metabolism
Mice, Inbred C57BL
Radiofrequency Ablation
/ methods
Triggering Receptor Expressed on Myeloid Cells-1
/ metabolism
Macrophages
/ metabolism
Humans
Male
Disease Progression
Tumor Microenvironment
Kupffer Cells
/ metabolism
Neoplasm Recurrence, Local
/ metabolism
Signal Transduction
HCC
HMGB1
Macrophage polarization
Radiofrequency ablation
Thermal injury
Tumor recurrence
Journal
Journal of cancer research and clinical oncology
ISSN: 1432-1335
Titre abrégé: J Cancer Res Clin Oncol
Pays: Germany
ID NLM: 7902060
Informations de publication
Date de publication:
28 Oct 2024
28 Oct 2024
Historique:
received:
03
05
2024
accepted:
12
10
2024
medline:
28
10
2024
pubmed:
28
10
2024
entrez:
28
10
2024
Statut:
epublish
Résumé
Tumor recurrence after radiofrequency ablation (RFA) affects the survival rate of patients and limits its clinical application. Tumor recurrence around the ablation area may be related to the thermal injury of hepatocytes (HCs) around the tumor, but the specific mechanism is still unclear. A liver cancer thermal injury mouse model was established via RFA in the C57BL/6 mice. Primary HCs and Kupffer cells (KCs) were isolated and cultured to assess their sensitivity to thermal injury via the MTT assay. Flow cytometry was used to assess macrophage polarization. Furthermore, Western blotting and co-immunoprecipitation (co-IP) were utilized to evaluate the protein expression of intracellular signaling pathway. Finally, Transwell and wound healing assays was conducted to evaluate the invasion potential of liver cancer cells. Our findings revealed that RFA-induced liver thermal injury promoted the upregulation and secretion of HMGB1 in HCs. HMGB1 had a protective effect on HCs thermal injury, potentially mediated through autophagy regulation. Heat-injured HCs release HMGB1, which activates the TREM1/JAK2/STAT3 signaling pathway in KCs, thus fostering an immunosuppressive tumor microenvironment (TME). Moreover, HMGB1 secretion by heat-injured HCs exacerbates the migration and invasion of HCC cells by influencing macrophage polarization. RFA-induced thermal injury triggers HMGB1 release from HCs, driving macrophage M2 polarization and increasing the invasion ability of liver cancer cells. These findings reveal a potential therapeutic target for combating liver cancer recurrence following thermal ablation.
Identifiants
pubmed: 39465435
doi: 10.1007/s00432-024-05996-9
pii: 10.1007/s00432-024-05996-9
doi:
Substances chimiques
HMGB1 Protein
0
Triggering Receptor Expressed on Myeloid Cells-1
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
480Subventions
Organisme : Chongqing Science and Health Joint Medical Research Project
ID : 2023MSXM046
Informations de copyright
© 2024. The Author(s).
Références
Arneth B (2019) Tumor Microenvironment. Med (Kaunas) 56:15. https://doi.org/10.3390/medicina56010015
doi: 10.3390/medicina56010015
Atri C, Guerfali FZ, Laouini D (2018) Role of human macrophage polarization in inflammation during infectious diseases. Int J Mol Sci 19:1801. https://doi.org/10.3390/ijms19061801
doi: 10.3390/ijms19061801
pubmed: 29921749
pmcid: 6032107
Biguetti CC, Cavalla F, Silveira EV, Tabanez AP, Francisconi CF, Taga R, Campanelli AP, Trombone APF, Rodrigues DC, Garlet GP (2019) HGMB1 and RAGE as essential components of Ti Osseointegration process in mice. Front Immunol 10:709. https://doi.org/10.3389/fimmu.2019.00709
doi: 10.3389/fimmu.2019.00709
pubmed: 31024546
pmcid: 6461067
Bosco MC, Raggi F, Varesio L (2016) Therapeutic potential of Targeting TREM-1 in Inflammatory diseases and Cancer. Curr Pharm Des 22:6209–6233. https://doi.org/10.2174/1381612822666160826110539
doi: 10.2174/1381612822666160826110539
pubmed: 27568730
Boutilier AJ, Elsawa SF (2021) Macrophage polarization States in the Tumor Microenvironment. Int J Mol Sci 22:6995. https://doi.org/10.3390/ijms22136995
doi: 10.3390/ijms22136995
pubmed: 34209703
pmcid: 8268869
Bruni D, Angell HK, Galon J (2020) The immune contexture and immunoscore in cancer prognosis and therapeutic efficacy. Nat Rev Cancer 20:662–680. https://doi.org/10.1038/s41568-020-0285-7
doi: 10.1038/s41568-020-0285-7
pubmed: 32753728
Chu KF, Dupuy DE (2014) Thermal ablation of tumours: biological mechanisms and advances in therapy. Nat Rev Cancer 14:199–208. https://doi.org/10.1038/nrc3672
doi: 10.1038/nrc3672
pubmed: 24561446
Dulmovits BM, Tang Y, Papoin J, He M, Li J, Yang H, Addorisio ME, Kennedy L, Khan M, Brindley E, Ashley RJ, Ackert-Bicknell C, Hale J, Kurita R, Nakamura Y, Diamond B, Barnes BJ, Hermine O, Gallagher PG, Steiner LA, Lipton JM, Taylor N, Mohandas N, Andersson U, Al-Abed Y, Tracey KJ, Blanc L (2022) HMGB1-mediated restriction of EPO signaling contributes to anemia of inflammation. Blood 139:3181–3193. https://doi.org/10.1182/blood.2021012048
doi: 10.1182/blood.2021012048
pubmed: 35040907
pmcid: 9136881
Funes SC, Rios M, Escobar-Vera J, Kalergis AM (2018) Implications of macrophage polarization in autoimmunity. Immunology 154:186–195. https://doi.org/10.1111/imm.12910
doi: 10.1111/imm.12910
pubmed: 29455468
pmcid: 5980179
Hernandez C, Huebener P, Pradere JP, Antoine DJ, Friedman RA, Schwabe RF (2018) HMGB1 links chronic liver injury to progenitor responses and hepatocarcinogenesis. J Clin Invest 128:2436–2451. https://doi.org/10.1172/jci91786
doi: 10.1172/jci91786
pubmed: 29558367
pmcid: 5983315
Jiang J, Chen S, Li K, Zhang C, Tan Y, Deng Q, Chai Y, Wang X, Chen G, Feng K, Zhang L, Xie CM, Ma K (2019) Targeting autophagy enhances heat stress-induced apoptosis via the ATP-AMPK-mTOR axis for hepatocellular carcinoma. Int J Hyperth 36:499–510. https://doi.org/10.1080/02656736.2019.1600052
doi: 10.1080/02656736.2019.1600052
Jiang C, Cai YQ, Yang JJ, Ma CY, Chen JX, Huang L, Xiang Z, Wu J (2023) Radiomics in the diagnosis and treatment of hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int 22:346–351. https://doi.org/10.1016/j.hbpd.2023.03.010
doi: 10.1016/j.hbpd.2023.03.010
pubmed: 37019775
Jube S, Rivera ZS, Bianchi ME, Powers A, Wang E, Pagano I, Pass HI, Gaudino G, Carbone M, Yang H (2012) Cancer cell secretion of the DAMP protein HMGB1 supports progression in malignant mesothelioma. Cancer Res 72:3290–3301. https://doi.org/10.1158/0008-5472.Can-11-3481
doi: 10.1158/0008-5472.Can-11-3481
pubmed: 22552293
pmcid: 3389268
Klune JR, Dhupar R, Cardinal J, Billiar TR, Tsung A (2008) HMGB1: endogenous danger signaling. Mol Med 14:476–484. https://doi.org/10.2119/2008-00034.Klune
doi: 10.2119/2008-00034.Klune
pubmed: 18431461
pmcid: 2323334
Li HM, Ye ZH (2017) Microenvironment of liver regeneration in liver cancer. Chin J Integr Med 23:555–560. https://doi.org/10.1007/s11655-017-2806-0
doi: 10.1007/s11655-017-2806-0
pubmed: 28523536
Li A, Ji B, Yang Y, Ye B, Zhu Q, Hu X, Liu Y, Zhou P, Liu J, Gao R, Zhou Q, Kang B, Jiang Y (2023) Single-cell RNA sequencing highlights the role of PVR/PVRL2 in the immunosuppressive tumour microenvironment in hepatocellular carcinoma. Front Immunol 14:1164448. https://doi.org/10.3389/fimmu.2023.1164448
doi: 10.3389/fimmu.2023.1164448
pubmed: 37383234
pmcid: 10293927
Liu Y, Tong Z, Li T, Chen Q, Zhuo L, Li W, Wu RC, Yu C (2012) Hepatitis B virus X protein stabilizes amplified in breast cancer 1 protein and cooperates with it to promote human hepatocellular carcinoma cell invasiveness. Hepatology 56:1015–1024. https://doi.org/10.1002/hep.25751
doi: 10.1002/hep.25751
pubmed: 22473901
Liu T, Zhao H, Wang Y, Qu P, Wang Y, Wu X, Zhao T, Yang L, Mao H, Peng L, Zhan Y, Li P (2024) Serum high mobility group box 1 as a potential biomarker for the progression of kidney disease in patients with type 2 diabetes. Front Immunol 15:1334109. https://doi.org/10.3389/fimmu.2024.1334109
doi: 10.3389/fimmu.2024.1334109
pubmed: 38481996
pmcid: 10932975
Luo YD, Fang L, Yu HQ, Zhang J, Lin XT, Liu XY, Wu D, Li GX, Huang D, Zhang YJ, Chen S, Jiang Y, Shuai L, He Y, Zhang LD, Bie P, Xie CM (2021) p53 haploinsufficiency and increased mTOR signalling define a subset of aggressive hepatocellular carcinoma. J Hepatol 74:96–108. https://doi.org/10.1016/j.jhep.2020.07.036
doi: 10.1016/j.jhep.2020.07.036
pubmed: 32738450
Ma L, Hernandez MO, Zhao Y, Mehta M, Tran B, Kelly M, Rae Z, Hernandez JM, Davis JL, Martin SP, Kleiner DE, Hewitt SM, Ylaya K, Wood BJ, Greten TF, Wang XW (2019) Tumor Cell Biodiversity drives Microenvironmental Reprogramming in Liver Cancer. Cancer Cell 36:418–430e6. https://doi.org/10.1016/j.ccell.2019.08.007
doi: 10.1016/j.ccell.2019.08.007
pubmed: 31588021
pmcid: 6801104
Na YR, Kim SW, Seok SH (2023) A new era of macrophage-based cell therapy. Exp Mol Med 55:1945–1954. https://doi.org/10.1038/s12276-023-01068-z
doi: 10.1038/s12276-023-01068-z
pubmed: 37653035
pmcid: 10545778
Otoo A, Czika A, Lamptey J, Yang JP, Feng Q, Wang MJ, Wang YX, Ding YB (2023) Emodin improves glucose metabolism and ovarian function in PCOS mice via the HMGB1/TLR4/NF-κB molecular pathway. Reproduction 166:323–336. https://doi.org/10.1530/rep-22-0449
doi: 10.1530/rep-22-0449
pubmed: 37651270
Ruzzenente A, Manzoni GD, Molfetta M, Pachera S, Genco B, Donataccio M, Guglielmi A (2004) Rapid progression of hepatocellular carcinoma after Radiofrequency ablation. World J Gastroenterol 10:1137–1140. https://doi.org/10.3748/wjg.v10.i8.1137
doi: 10.3748/wjg.v10.i8.1137
pubmed: 15069713
pmcid: 4656348
Seki T, Tamai T, Ikeda K, Imamura M, Nishimura A, Yamashiki N, Nakagawa T, Inoue K (2001) Rapid progression of hepatocellular carcinoma after transcatheter arterial chemoembolization and percutaneous radiofrequency ablation in the primary tumour region. Eur J Gastroenterol Hepatol 13:291–294. https://doi.org/10.1097/00042737-200103000-00014
doi: 10.1097/00042737-200103000-00014
pubmed: 11293452
Shin SW, Ahn KS, Kim SW, Kim TS, Kim YH, Kang KJ (2021) Liver resection Versus local ablation therapies for Hepatocellular Carcinoma within the Milan Criteria: a systematic review and Meta-analysis. Ann Surg 273:656–666. https://doi.org/10.1097/sla.0000000000004350
doi: 10.1097/sla.0000000000004350
pubmed: 33074898
Visioni A, Skitzki J (2016) Technical considerations for the generation of Adoptively Transferred T cells in Cancer Immunotherapy. Cancers (Basel) 8:86. https://doi.org/10.3390/cancers8090086
doi: 10.3390/cancers8090086
pubmed: 27657129
Vitale I, Manic G, Coussens LM, Kroemer G, Galluzzi L (2019) Macrophages and metabolism in the Tumor Microenvironment. Cell Metab 30:36–50. https://doi.org/10.1016/j.cmet.2019.06.001
doi: 10.1016/j.cmet.2019.06.001
pubmed: 31269428
Wang S, Zhang Y (2020) HMGB1 in inflammation and cancer. J Hematol Oncol 13:116. https://doi.org/10.1186/s13045-020-00950-x
doi: 10.1186/s13045-020-00950-x
pubmed: 32831115
pmcid: 7443612
Wang X, Xiang L, Li H, Chen P, Feng Y, Zhang J, Yang N, Li F, Wang Y, Zhang Q, Li F, Cao F (2015) The role of HMGB1 signaling pathway in the Development and Progression of Hepatocellular Carcinoma: a review. Int J Mol Sci 16:22527–22540. https://doi.org/10.3390/ijms160922527
doi: 10.3390/ijms160922527
pubmed: 26393575
pmcid: 4613322
Wei H, Li W, Yang M, Fang Q, Nian J, Huang Y, Wei Q, Huang Z, Liu G, Xu Z, Hu A, Pu J (2024) METTL3/16-mediated m(6)a modification of ZNNT1 promotes hepatocellular carcinoma progression by activating ZNNT1/osteopontin/S100A9 positive feedback loop-mediated crosstalk between macrophages and tumour cells. Clin Immunol 261:109924. https://doi.org/10.1016/j.clim.2024.109924
doi: 10.1016/j.clim.2024.109924
pubmed: 38310994
Wu J, Guo W, Lin SZ, Wang ZJ, Kan JT, Chen SY, Zhu YZ (2016) Gp130-mediated STAT3 activation by S-propargyl-cysteine, an endogenous hydrogen sulfide initiator, prevents doxorubicin-induced cardiotoxicity. Cell Death Dis 7:e2339. https://doi.org/10.1038/cddis.2016.209
doi: 10.1038/cddis.2016.209
pubmed: 27537522
pmcid: 5108313
Wu K, Lin K, Li X, Yuan X, Xu P, Ni P, Xu D (2020) Redefining Tumor-Associated macrophage subpopulations and functions in the Tumor Microenvironment. Front Immunol 11:1731. https://doi.org/10.3389/fimmu.2020.01731
doi: 10.3389/fimmu.2020.01731
pubmed: 32849616
pmcid: 7417513
Wyganowska-Swiatkowska M, Nohawica M, Grocholewicz K, Nowak G (2020) Influence of Herbal Medicines on HMGB1 release, SARS-CoV-2 viral attachment, Acute Respiratory failure, and Sepsis. A literature review. Int J Mol Sci 21:4639. https://doi.org/10.3390/ijms21134639
doi: 10.3390/ijms21134639
pubmed: 32629817
pmcid: 7370028
Xu Z, Ma W, Wang J, Chen H, Li H, Yin Z, Hao J, Chen K (2024) Nuclear HMGB1 is critical for CD8 T cell IFN-γ production and anti-tumor immunity. Cell Rep 43:114591. https://doi.org/10.1016/j.celrep.2024.114591
doi: 10.1016/j.celrep.2024.114591
pubmed: 39116204
Yan Y, Zhang LB, Ma R, Wang MN, He J, Wang PP, Tao QW, Xu Y (2024) Jolkinolide B ameliorates rheumatoid arthritis by regulating the JAK2/STAT3 signaling pathway. Phytomedicine 124:155311. https://doi.org/10.1016/j.phymed.2023.155311
doi: 10.1016/j.phymed.2023.155311
pubmed: 38199156
Yan L, Wang J, Cai X, Liou YC, Shen HM, Hao J, Huang C, Luo G, He W (2024a) Macrophage plasticity: signaling pathways, tissue repair, and regeneration. MedComm (2020) 5:e658. https://doi.org/10.1002/mco2.658
Yao W, Tao R, Wang K, Ding X (2024) Icariin attenuates vascular endothelial dysfunction by inhibiting inflammation through GPER/Sirt1/HMGB1 signaling pathway in type 1 diabetic rats. Chin J Nat Med 22:293–306. https://doi.org/10.1016/s1875-5364(24)60618-7
doi: 10.1016/s1875-5364(24)60618-7
pubmed: 38658093
Zeng J, Lin Z, Tang J, Chen X, Huang K, Gan F (2024) The role of JAK2/STAT3 pathway in non-cytotoxic concentrations of DON-induced aggravation of inflammatory response in IL-10 deficient RAW264.7 cells. Food Chem Toxicol 186:114557. https://doi.org/10.1016/j.fct.2024.114557
doi: 10.1016/j.fct.2024.114557
pubmed: 38432439
Zhang S, Huang Y, Pi S, Chen H, Ye F, Wu C, Li L, Ye Q, Lin Y, Su Z (2023) Autophagy-amplifying nanoparticles evoke immunogenic cell death combined with anti-PD-1/PD-L1 for residual tumors immunotherapy after RFA. J Nanobiotechnol 21:360. https://doi.org/10.1186/s12951-023-02067-y
doi: 10.1186/s12951-023-02067-y
Zhao Y, Bai J, Wang X, Zhang Y, Yan X, Qi J, Xia X, Feng Y, Duan B (2024) Threatment strategies for recurrent Hepatocellular Carcinoma patients: ablation and its combination patterns. J Cancer 15:2193–2205. https://doi.org/10.7150/jca.93885
doi: 10.7150/jca.93885
pubmed: 38495485
pmcid: 10937274
Žūkienė R, Naučienė Z, Šilkūnienė G, Vanagas T, Gulbinas A, Zimkus A, Mildažienė V (2017) Contribution of mitochondria to injury of hepatocytes and liver tissue by hyperthermia. Med (Kaunas) 53:40–49. https://doi.org/10.1016/j.medici.2017.01.001
doi: 10.1016/j.medici.2017.01.001