ArticleProceedings of the National Academy of Sciences of the United States of America2022
Metabolic reprogramming of tumor-associated macrophages by collagen turnover promotes fibrosis in pancreatic cancer.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 108 citations in OpenAlex.
- IGF1-IGF1R signaling in tumor-associated macrophages regulates extracellular matrix organization in BRAF inhibitor-targeted melanoma.Molecular and cellular biochemistry · 2026Article
- Deoxythymidylate Kinase (DTYMK)-Driven Pyrimidine Hypermetabolism Is Associated with a Folate-Dependent Macrophage Programme in Triple-Negative Breast Cancer.International journal of molecular sciences · 2026Article
- Extracellular Matrix Remodeling in Tumors: Forces Beyond Fibroblasts.Cancer research · 2026Article
- Review
- Breast cancer cell-derived extracellular vesicles accelerate collagen fibrillogenesis and integrate into the matrix.Materials today. Bio · 2026Article
- Spatial Multiomics Analyses Reveal That Diabetes Promotes Pancreatic Cancer Progression by Stimulating Cholesterol-Induced Neutrophil Extracellular Trap Formation.Cancer research · 2026Article
- Therapeutic Potential of Lentiviral miR-200a Mimics in Regulating Fibrinolysis and EMT Markers During Pulmonary Fibrosis.FASEB bioAdvances · 2026Article
- Heterocellular crosstalk and architecture of the pancreatic tumour microenvironment.Nature reviews. Cancer · 2026Review
- COL3A1NPJ precision oncology · 2026Article
- Engineered bone matrix models for understanding breast cancer skeletal metastasis.Cancer metastasis reviews · 2026Review
- Single-cell transcriptomic analysis of cutaneous squamous cell carcinoma identifies an NR1H3-associated angiogenic macrophage state.Frontiers in immunology · 2026Article
- Tumor-immune metabolic tug-of-war: from immune escape to targeting metabolic rewiring in cancer therapy.Frontiers in cell and developmental biology · 2026Review
- Shikonin in Hepatocellular Carcinoma: Bridging Metabolic Disruption and Immunomodulation.Journal of hepatocellular carcinoma · 2026Review
- Is there a link between fascia and cancer? From potential mechanisms to future treatment options.Frontiers in physiology · 2026Review
- Protein arginine methyltransferase 5 as a novel therapeutic target in solid tumors.Genes & diseases · 2026Review
- Dynamic Evolution of the Tumor Immune Microenvironment in Malignant Tumors and Emerging Therapeutic Paradigms.MedComm · 2025Review
- Review
- NC410, a bivalent LAIR-2 construct, remodels collagen in the tumor microenvironment and abrogates neutrophil-driven T cell suppression.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- SPP1 + macrophages facilitate pancreatic cancer progression via ITGB6-mediated interactions: evidence from integrated multi-omics analysis and experimental validation.Immunologic research · 2025Article
- Proteomics in pancreatic cancer.Biomarker research · 2025Review
14 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
A hallmark of pancreatic tumors is their highly desmoplastic stroma composed of fibroblasts, immune cells, and a dense network of collagen fibers. Tumor-associated macrophages are one of the most abundant immune cell populations in the pancreatic tumor stroma. Their protumorigenic function has been attributed predominantly to their capacity to promote immune evasion and metastasis. Tumor-assoc iated macrophages are also well known for their role in the remodeling of the stroma via collagen production and degradation, with the latter being mediated by mannose receptor (MRC1)-dependent endocytosis of collagen. Here we show that MRC1-mediated collagen internalization and subsequent lysosomal degradation by macrophages harboring a tumor-associated phenotype are accompanied by the accumulation of collagen-derived intracellular free amino acids and increased arginine biosynthesis. The resulting increase in intracellular arginine levels leads to the up-regulation of inducible nitric oxide synthase and the production of reactive nitrogen species. Furthermore, reactive nitrogen species derived from internalized and degraded collagen promotes a profibrotic phenotype in pancreatic stellate cells resulting in enhanced intratumoral collagen deposition. Overall, our findings identify a role for extracellular matrix remodeling in the functional modulation of tumor-associated macrophages via metabolic rewiring.
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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.