ArticleScientific reports2015
Morphine Modulates Interleukin-4- or Breast Cancer Cell-induced Pro-metastatic Activation of Macrophages.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 2 of them syntheses that pooled it.
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The trial behind it
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
38 citing papers in PubMed, 2 syntheses or guidelines pooled it, 68 citations in OpenAlex.
- Opioid use and the risk of cancer incidence and mortality: a systematic review.Cancer metastasis reviews · 2025Pooled it
- The organ-specific modulation of malignant processes by opioids: a systematic review of cell culture studies.British journal of cancer · 2025Pooled it
- Opioid-free anesthesia attenuates perioperative immunosuppression by regulating macrophages polarization in gastric cancer patients treated with neoadjuvant PD-1 inhibitor.Frontiers in immunology · 2024Trial
- Influence of exogenous opioids on the acute inflammatory response in the perioperative period of oncological surgery: a clinical study.Brazilian journal of anesthesiology (Elsevier)Trial
- Crosstalk Between Opioids and the Anti-Tumour Immune Checkpoint Axis.Current oncology (Toronto, Ont.) · 2026Review
- Antitumor effects of morphine and tramadol on lung metastasis of melanoma tumor cells in vitro and in vivo.Medical oncology (Northwood, London, England) · 2025Article
- Research progress on the impact of opioids on the tumor immune microenvironment (Review).Molecular and clinical oncology · 2025Review
- Impact of opioids and mu-opioid receptors on oncologic metastasis.American journal of cancer research · 2024Review
- Role of Endorphins in Breast Cancer Pathogenesis and Recovery.Advances in neurobiology · 2024Article
- Immunomodulatory properties of morphine and the hypothesised role of long-term opioid use in the immunopathogenesis of tuberculosis.Frontiers in immunology · 2023Review
- Inhibition of CDK8/19 Mediator kinase potentiates HER2-targeting drugs and bypasses resistance to these agents in vitro and in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Macrophage circadian rhythms are differentially affected based on stimuli.Integrative biology : quantitative biosciences from nano to macro · 2022Article
- IL4/IL4R signaling promotes the osteolysis in metastatic bone of CRC through regulating the proliferation of osteoclast precursors.Molecular medicine (Cambridge, Mass.) · 2021Article
- Targeting the mu-Opioid Receptor for Cancer Treatment.Current oncology reports · 2021Review
- Opioids Regulate the Immune System: Focusing on Macrophages and Their Organelles.Frontiers in pharmacology · 2021Review
- Opioid Receptor-Mediated and Non-Opioid Receptor-Mediated Roles of Opioids in Tumour Growth and Metastasis.Frontiers in oncology · 2021Review
- Unintended Effects of GPCR-Targeted Drugs on the Cancer Phenotype.Trends in pharmacological sciences · 2020Review
- Opioid-Mediated HIV-1 Immunopathogenesis.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2020Review
- The role of macrophages during breast cancer development and response to chemotherapy.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2020Review
- HDAC8 inhibitor attenuates airway responses to antigen stimulus through synchronously suppressing galectin-3 expression and reducing macrophage-2 polarization.Respiratory research · 2020Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interactions between cancer cells and stromal cells in the tumour microenvironment play a key role in the control of invasiveness, metastasis and angiogenesis. Macrophages display a range of activation states in specific pathological contexts and alternatively activated (M2) macrophages can promote tumour aggressiveness. Opioids are able to modulate tumour growth and metastasis. We tested whether morphine modulates the activation of macrophages induced by (i) interleukin-4 (IL-4), the prototypical M2 polarization-inducing cytokine, or (ii) coculture with breast cancer cells. We showed that IL-4 causes increased MMP-9 production and expression of the alternative activation markers arginase-1 and MRC-1. Morphine prevented IL-4-induced increase in MMP-9 in a naloxone- and methylnaltrexone-reversible fashion. Morphine also prevented IL-4-elicited alternative activation of RAW264.7 macrophages. Expression of MMP-9 and arginase-1 were increased when RAW264.7 were subjected to paracrine activation by 4T1 cells, and this effect was prevented by morphine via an opioid receptor-mediated mechanism. Morphine further decreased 4T1 breast cancer cell invasion elicited by co-culture with RAW264.7. Reduction of MMP-9 expression and alternative activation of macrophages by morphine was confirmed using mouse bone marrow-derived macrophages. Taken together, our results indicate that morphine may modulate tumour aggressiveness by regulating macrophage protease production and M2 polarization within the tumour microenvironment.
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Registered trials
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.