ArticleProceedings of the National Academy of Sciences of the United States of America2016
Tumor-associated fibroblasts predominantly come from local and not circulating precursors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 154 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
154 citing papers in PubMed, 220 citations in OpenAlex.
- Metabolic heterogeneity and functional diversity of cancer-associated fibroblasts in gastric cancer (Review).Oncology letters · 2026Review
- Molecular phenotypes and spatial archetypes: A new framework for cancer-associated fibroblasts.Cancer cell · 2026Review
- The exosomal miRNA/FOXN3 axis empowers fibroblasts with tumor-promoting functions via enhanced migration and altered secretome.Journal of nanobiotechnology · 2026Article
- Nanomaterials targeting cancer-associated fibroblasts to overcome stromal barriers in cancer immunotherapy.Journal of nanobiotechnology · 2026Review
- In vitro models of cancer-associated fibroblast heterogeneity uncover subtype-specific effects of CRISPR perturbations.Molecular oncology · 2026Article
- Cancer-Associated Fibroblasts Functions as Multifunctional Architects of the Tumor Stroma and Represent Emerging Therapeutic Vulnerabilities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- The tumor-associated fibroblasts regulate urothelial carcinoma progression.Journal of molecular cell biology · 2026Article
- Circulating Thrombospondin-4-Positive Fibroblasts Might be a Useful Marker for Diagnosis of Gastric Cancer.Cancer medicine · 2026Article
- NGF-mediated tumor-stroma crosstalk promotes prostate cancer aggressiveness.Journal of translational medicine · 2026Article
- Mapping the Tissue-of-Origins of Mesenchymal Stromal Cells in Injury Repair.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Navigating the Tumor Microenvironment in Colorectal Liver Metastasis: Barriers to Therapy and Emerging Opportunities.Oncology research · 2026Review
- Hotspots and frontiers of the relationship between hepatocellular carcinoma and cancer-associated fibroblasts: a bibliometric analysis and review.Discover oncology · 2025Article
- Cancer-associated fibroblasts in the tumor microenvironment: heterogeneity, crosstalk mechanisms, and therapeutic implications.Molecular cancer · 2025Review
- Extracellular Vesicle-Packaged circTAX1BP1 from Cancer-Associated Fibroblasts Regulates RNA m6A Modification through Lactylation of VIRMA in Colorectal Cancer Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Cancer-Associated Fibroblasts: Origin, Classification, Tumorigenicity, and Targeting for Cancer Therapy.MedComm · 2025Review
- Detection of Circulating Cancer-Associated Fibroblasts in Head and Neck Squamous Cell Carcinoma and Their Impact on Circulating Tumor Cells.Head & neck · 2025Article
- Inhibition of ACVR1 in Cancer-Associated Fibroblasts Suppresses Colorectal Cancer Cell Growth.Annals of surgical oncology · 2025Article
- Role of exosomal non‑coding RNAs in cancer‑associated fibroblast‑mediated therapy resistance (Review).International journal of oncology · 2025Review
- The Role of Organoids in Advancing Colorectal Cancer Research: Insights and Future Directions.Cancers · 2025Review
- Overcoming cancer treatment resistance: Unraveling the role of cancer-associated fibroblasts.Journal of the National Cancer Center · 2025Review
94 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Fibroblasts are common cell types in cancer stroma and lay down collagen required for survival and growth of cancer cells. Although some cancer therapy strategies target tumor fibroblasts, their origin remains controversial. Multiple publications suggest circulating mesenchymal precursors as a source of tumor-associated fibroblasts. However, we show by three independent approaches that tumor fibroblasts derive primarily from local, sessile precursors. First, transplantable tumors developing in a mouse expressing green fluorescent reporter protein (EGFP) under control of the type I collagen (Col-I) promoter (COL-EGFP) had green stroma, whereas we could not find COL-EGFP(+) cells in tumors developing in the parabiotic partner lacking the fluorescent reporter. Lack of incorporation of COL-EGFP(+) cells from the circulation into tumors was confirmed in parabiotic pairs of COL-EGFP mice and transgenic mice developing autochthonous intestinal adenomas. Second, transplantable tumors developing in chimeric mice reconstituted with bone marrow cells from COL-EGFP mice very rarely showed stromal fibroblasts expressing EGFP. Finally, cancer cells injected under full-thickness COL-EGFP skin grafts transplanted in nonreporter mice developed into tumors containing green stromal cells. Using multicolor in vivo confocal microscopy, we found that Col-I-expressing fibroblasts constituted approximately one-third of the stromal mass and formed a continuous sheet wrapping the tumor vessels. In summary, tumors form their fibroblastic stroma predominantly from precursors present in the local tumor microenvironment, whereas the contribution of bone marrow-derived circulating precursors is rare.
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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.