ArticleOncotarget2015
Metformin prevents cancer metastasis by inhibiting M2-like polarization of tumor associated macrophages.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers, 3 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
99 citing papers in PubMed, 3 syntheses or guidelines pooled it, 158 citations in OpenAlex.
- Prognostic Significance of Tumor-Associated Macrophage Content in Head and Neck Squamous Cell Carcinoma: A Meta-Analysis.Frontiers in oncology · 2019Pooled it
- Metformin Use and Lung Cancer Risk in Diabetic Patients: A Systematic Review and Meta-Analysis.Disease markers · 2019 · on this mapPooled it
- Metformin therapy associated with survival benefit in lung cancer patients with diabetes.Oncotarget · 2016 · on this mapPooled it
- Phase II trial of nivolumab and metformin in patients with treatment-refractory microsatellite stable metastatic colorectal cancer.Journal for immunotherapy of cancer · 2023Trial
- Macrophage polarization plasticity in pulmonary fibrosis: a review from pathogenesis to therapeutic targeting.Inflammopharmacology · 2026Review
- Therapeutic repurposing of old drugs to modulate the tumor immune microenvironment and enhance immunotherapy efficacy.Journal of pharmaceutical analysis · 2026Review
- Metformin as an Innate Immune Modulator: Metabolic and Epigenetic Reprogramming of Innate Immune Cells and Therapeutic Implications.Current issues in molecular biology · 2026Review
- Macrophages in lung cancer: principal factors, regulatory mechanisms, and therapeutic opportunities: a narrative review.Translational lung cancer research · 2026Review
- Obesity-derived metabolites modulate anti-tumor immunity in the tumor microenvironment: from mechanisms to clinical applications.BMC medicine · 2026Review
- Metformin as a potential therapeutic agent in broken heart syndrome: Targeting AMPK-dependent cardio-protection and microvascular function.Molecular biology reports · 2026Review
- Effect of metformin on inflammation and bone damage in a rat model of medication-related osteonecrosis of the jaw.European journal of oral sciences · 2026Article
- Metformin modulates the phenotypes of tumor-associated macrophages in glioblastoma in a context-dependent manner by promoting the homeostasis of macrophages.Frontiers in oncology · 2026Article
- Glioma tumor microenvironment and immunotherapy: past, present, and future.Biomarker research · 2025Review
- Myeloid metabolism and its role in immunotherapy of cancer.Journal for immunotherapy of cancer · 2025Review
- The mechanism of action and therapeutic potential of tumor-associated macrophages in tumor immune evasion.Frontiers in immunology · 2025Review
- Review
- Advances in the Use of Metformin for Liver Disease.Current medicinal chemistry · 2025Review
- The Immune Landscape of Pheochromocytoma and Paraganglioma: Current Advances and Perspectives.Endocrine reviews · 2024Review
- Respiratory complex I regulates dendritic cell maturation in explant model of human tumor immune microenvironment.Journal for immunotherapy of cancer · 2024Article
- Metformin Alters Tumor Immune Microenvironment, Improving the Outcomes of Breast Cancer Patients With Type 2 Diabetes Mellitus.Journal of breast cancer · 2024Article
39 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
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accumulated evidence suggests that M2-like polarized tumor associated macrophages (TAMs) plays an important role in cancer progression and metastasis, establishing TAMs, especially M2-like TAMs as an appealing target for therapy intervention. Here we found that metformin significantly suppressed IL-13 induced M2-like polarization of macrophages, as illustrated by reduced expression of CD206, down-regulation of M2 marker mRNAs, and inhibition of M2-like macrophages promoted migration of cancer cells and endothelial cells. Metformin triggered AMPKα1 activation in macrophage and silencing of AMPKα1 partially abrogated the inhibitory effect of metformin in IL-13 induced M2-like polarization. Administration of AICAR, another activator of AMPK, also blocked the M2-like polarization of macrophages. Metformin greatly reduced the number of metastases of Lewis lung cancer without affecting tumor growth. In tumor tissues, the percentage of M2-like macrophage was decreased and the area of pericyte-coated vessels was increased. Further, the anti-metastatic effect of metformin was abolished when the animals were treated with macrophages eliminating agent clodronate liposome. These findings suggest that metformin is able to block the M2-like polarization of macrophages partially through AMPKα1, which plays an important role in metformin inhibited metastasis of Lewis lung cancer.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.