ArticleJournal of experimental & clinical cancer research : CR2016
Deletion of interleukin-6 in monocytes/macrophages suppresses the initiation of hepatocellular carcinoma in mice.
Article in Journal of experimental & clinical cancer research : CR, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers, 1 of them a synthesis that pooled it.
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Who cites it
101 citing papers in PubMed, 1 synthesis or guideline pooled it, 138 citations in OpenAlex.
- Physical Activity and Risk of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.Digestive diseases and sciences · 2023Pooled it
- The macrophage opera: from metabolic prolog to oncogenic crescendo in metabolic dysfunction-associated steatotic liver disease.Frontiers in medicine · 2026Review
- Blockade of CC chemokine receptor 2 suppresses pancreatic cancer progression through the interaction with macrophages in the tumor microenvironment.Scientific reports · 2025Article
- Transforming growth factor-β1 triggers the proliferation of human cholangiocyte spheroids via interleukin-6-mediated STAT3 signaling.Molecular biology reports · 2025Article
- MEF2D-expressing cancer precursors reprogram tissue-resident macrophages to support liver tumorigenesis.Nature cancer · 2025Article
- Review
- Deletion of Tfap2a in hepatocytes and macrophages promotes the progression of hepatocellular carcinoma by regulating SREBP1/FASN/ACC pathway and anti-inflammatory effect of IL10.Cell death & disease · 2025Article
- Article
- Review
- Article
- Does depressurization of the portal vein before liver transplantation affect the recurrence of HCC? A nested case-control study.BMC cancer · 2024Article
- Integrating Network Pharmacology and Experimental Validation to Decipher the Mechanism of Action ofDrug design, development and therapy · 2024Article
- Forces at play: exploring factors affecting the cancer metastasis.Frontiers in immunology · 2024Review
- The role of tumor-associated macrophages in hepatocellular carcinoma progression: A narrative review.Cancer medicine · 2023Review
- Inflammation in Prostate Cancer: Exploring the Promising Role of Phenolic Compounds as an Innovative Therapeutic Approach.Biomedicines · 2023Review
- Targeting the Heterogeneous Tumour-Associated Macrophages in Hepatocellular Carcinoma.Cancers · 2023Review
- Communicator Extraordinaire: Extracellular Vesicles in the Tumor Microenvironment Are Essential Local and Long-Distance Mediators of Cancer Metastasis.Biomedicines · 2023Review
- Hollow Mesoporous Silica Nanoparticles for Dual Chemo-starvation Therapy of Hepatocellular Carcinoma.Pharmaceutical research · 2023Article
- Induction of Skin Cancer by Long-Term Blue Light Irradiation.Biomedicines · 2023Article
- Immune System and Hepatocellular Carcinoma (HCC): New Insights into HCC Progression.International journal of molecular sciences · 2023Review
41 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHepatocellular carcinoma (HCC) is associated with inflammation, and roughly 30 % of the global population shows serological evidence of current or past infection with hepatitis B or hepatitis C virus. Resident hepatic macrophages, known as Kupffer cells (KCs), are considered as the specific tumor-associated macrophages (TAMs) of HCC, and can produce various cytokines-most importantly interleukin (IL)-6-to promote tumorigenesis of HCC. However, the roles of KCs and IL-6 in carcinogenesis in the liver are still unclear.
methodsWe analyzed leukocyte-related peripheral blood data of 192 patients and constructed a mouse model in which the bone marrow was cleared out by irradiation and reconstructed using bone marrow donated from IL-6-deficient mice to further elucidate the hepatic pathological changes in response to toxic challenge and oncogenic gene mutation.
resultsPeripheral monocyte counts and serum IL-6 levels were significantly higher in patients with HCC than in those without HCC. In addition, there was a significant difference in the levels of IL-6 among individuals with different histopathological grades. In mice with selective IL-6 ablation in monocytes/KCs, we observed decreased toxic liver injury, inflammatory infiltration, and systemic inflammation. In Mdr2-deficient mice, which spontaneously developed HCC, the loss of IL-6 in monocytes/KCs resulted in inhibition of IL-6/signal transducer and activator of transcription 3 signaling, decreased serum IL-6 levels, and delayed tumorigenesis.
conclusionsOur findings demonstrate that increased TAM-derived IL-6 had an amplifying effect on the inflammation response, thereby promoting the occurrence and development of HCC.
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