ArticleJournal of immunology (Baltimore, Md. : 1950)2011
Regulation of macrophage arginase expression and tumor growth by the Ron receptor tyrosine kinase.
Article in Journal of immunology (Baltimore, Md. : 1950), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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Who cites it
85 citing papers in PubMed, 136 citations in OpenAlex.
- Nitrogen Isotope Effects in Urea Metabolism: From Biochemistry toInternational journal of molecular sciences · 2026Review
- Macrophage-intrinsic and IL-9-dependent arginine metabolism promotes lung tumor growth.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- MSP-RON signaling in liver pathobiology and as an emerging therapeutic target: a review of the current evidence.Cell communication and signaling : CCS · 2025Review
- Immunization with Complete Freund's Adjuvant Reveals Trained Immunity-like Features in A/J Mice.Vaccines · 2025Article
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- Cell of origin alters myeloid-mediated immunosuppression in lung adenocarcinoma.bioRxiv : the preprint server for biology · 2024Article
- Melatonin modulates L-arginine metabolism in tumor-associated macrophages by targeting arginase 1 in lymphoma.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Genome-scale modeling predicts metabolic differences between macrophage subtypes in colorectal cancer.iScience · 2023Article
- Review
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- Ensemble-based genome-scale modeling predicts metabolic differences between macrophage subtypes in colorectal cancer.bioRxiv : the preprint server for biology · 2023Article
- IL-6/ERK signaling pathway participates in type I IFN-programmed, unconventional M2-like macrophage polarization.Scientific reports · 2023Article
- Immune checkpoint blockade in pancreatic cancer: Trudging through the immune desert.Seminars in cancer biology · 2022Review
- Race and prostate cancer: genomic landscape.Nature reviews. Urology · 2022Review
- Cancer cell targeting by CAR-T cells: A matter of stemness.Frontiers in molecular medicine · 2022Review
- Metabolic Regulation of Macrophage Activation.Journal of innate immunity · 2022Review
- Current Perspectives on the Immunosuppressive Niche and Role of Fibrosis in Hepatocellular Carcinoma and the Development of Antitumor Immunity.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2022Review
- Macrophage-mediated RON signaling supports breast cancer growth and progression through modulation of IL-35.Oncogene · 2022Article
- Blocking Short-Form Ron Eliminates Breast Cancer Metastases through Accumulation of Stem-Like CD4+ T Cells That Subvert Immunosuppression.Cancer discovery · 2021Article
- Metabolic Strategies for Inhibiting Cancer Development.Advances in nutrition (Bethesda, Md.) · 2021Review
25 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 3 countries.
Funding
Abstract
M1 activation of macrophages promotes inflammation and immunity to intracellular pathogens, whereas M2 macrophage activation promotes resolution of inflammation, wound healing, and tumor growth. These divergent phenotypes are characterized, in part, by the expression of inducible NO synthase and arginase I (Arg1) in M1 versus M2 activated macrophages, respectively. In this study, we demonstrate that the Ron receptor tyrosine kinase tips the balance of macrophage activation by attenuating the M1 phenotype while promoting expression of Arg1 through a Stat6-independent mechanism. Induction of the Arg1 promoter by Ron is mediated by an AP-1 site located 433 bp upstream of the transcription start site. Treatment of primary macrophages with macrophage stimulating protein, the ligand for Ron, induces potent MAPK activation, upregulates Fos, and enhances binding of Fos to the AP-1 site in the Arg1 promoter. In vivo, Arg1 expression in tumor-associated macrophages (TAMs) from Ron(-/-) mice was significantly reduced compared with that in TAMs from control animals. Furthermore, we show that Ron is expressed specifically by Tie2-expressing macrophages, a TAM subset that exhibits a markedly skewed M2 and protumoral phenotype. Decreased Arg1 in TAMs from Ron(-/-) mice was associated with reduced syngeneic tumor growth in these animals. These findings indicate that Ron induces Arg1 expression in macrophages through a previously uncharacterized AP-1 site in the Arg1 promoter and that Ron could be therapeutically targeted in the tumor microenvironment to inhibit tumor growth by targeting expression of Arg1.
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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.