ArticleCancer research2016
Macrophage Infiltration and Alternative Activation during Wound Healing Promote MEK1-Induced Skin Carcinogenesis.
Article in Cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 42 citations in OpenAlex.
- Macrophages: Subtypes, Distribution, Polarization, Immunomodulatory Functions, and Therapeutics.MedComm · 2025Review
- METTL14/YTHDF2 m6A Axis Protects Against M2 Macrophage Polarization in Endometriosis by Regulating KLF4 Stability.Applied biochemistry and biotechnology · 2025Article
- Article
- The paradoxical activity of BRAF inhibitors: potential use in wound healing.Archives of dermatological research · 2025Review
- Caspase-8-dependent autophagy regulates neutrophil infiltration in oral squamous cell carcinoma.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Monitoring Macrophage Polarization with Gene Expression Reporters and Bioluminescence Phasor Analysis.Chemical & biomedical imaging · 2024Article
- Eutopic and Ectopic Endometrial Interleukin-17 and Interleukin-17 Receptor Expression at the Endometrial-Myometrial Interface in Women with Adenomyosis: Possible Pathophysiology Implications.International journal of molecular sciences · 2024Article
- Monitoring macrophage polarization with gene expression reporters and bioluminescence phasor analysis.bioRxiv : the preprint server for biology · 2024Article
- Reproducible strategy for excisional skin-wound-healing studies in mice.Nature protocols · 2024Review
- Reduced smooth muscle-fibroblasts transformation potentially decreases intestinal wound healing and colitis-associated cancer in ageing mice.Signal transduction and targeted therapy · 2023Article
- Nanoparticle-based drug delivery systems to enhance cancer immunotherapy in solid tumors.Frontiers in immunology · 2023Review
- Targeting tumor-associated macrophage: an adjuvant strategy for lung cancer therapy.Frontiers in immunology · 2023Review
- Production and Characterization of Exopolysaccharide From Newly Isolated Marine ProbioticFrontiers in microbiology · 2022Article
- IL-17: an important pathogenic factor in endometriosis.International journal of medical sciences · 2022Review
- Review
- Research trends in pharmacological modulation of tumor-associated macrophages.Clinical and translational medicine · 2021Review
- Pro-tumorigenic functions of macrophages at the primary, invasive and metastatic tumor site.Cancer immunology, immunotherapy : CII · 2020Review
- Development, Characterization and Use of Liposomes as Amphipathic Transporters of Bioactive Compounds for Melanoma Treatment and Reduction of Skin Inflammation: A Review.International journal of nanomedicine · 2020Review
- IL-17A Modulates Peritoneal Macrophage Recruitment and M2 Polarization in Endometriosis.Frontiers in immunology · 2020Article
- Essential Oil ofMolecules (Basel, Switzerland) · 2019Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Macrophages are essential for the progression and maintenance of many cancers, but their role during the earliest stages of tumor formation is unclear. To test this, we used a previously described transgenic mouse model of wound-induced skin tumorigenesis, in which expression of constitutively active MEK1 in differentiating epidermal cells results in chronic inflammation (InvEE mice). Upon wounding, the number of epidermal and dermal monocytes and macrophages increased in wild-type and InvEE skin, but the increase was greater, more rapid, and more sustained in InvEE skin. Macrophage ablation reduced tumor incidence. Furthermore, bioluminescent imaging in live mice to monitor macrophage flux at wound sites revealed that macrophage accumulation was predictive of tumor formation; wounds with the greatest number of macrophages at day 5 went on to develop tumors. Gene expression profiling of flow-sorted monocytes, macrophages, and T cells from InvEE and wild-type skin showed that as wound healing progressed, InvEE macrophages altered their phenotype. Throughout wound healing and after wound closure, InvEE macrophages demonstrated sustained upregulation of several markers implicated in alternative macrophage activation including arginase-1 (ARG1) and mannose receptor (CD206). Notably, inhibition of ARG1 activity significantly reduced tumor formation and epidermal proliferation in vivo, whereas addition of L-arginase to cultured keratinocytes stimulated proliferation. We conclude that macrophages play a key role in early, inflammation-mediated skin tumorigenesis, with mechanistic evidence suggesting that ARG1 secretion drives tumor development by stimulating epidermal cell proliferation. These findings highlight the importance of cancer immunotherapies aiming to polarize tumor-associated macrophages toward an antitumor phenotype.
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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.