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Tumor-associated fibroblasts predominantly come from local and not circulating precursors
Open accessAbstract
Significance: Fibroblasts constitute an important element of tumors and have received considerable attention in recent years due to their tumor-promoting and immunosuppressive properties. As a consequence, tumor-associated fibroblasts (TAFs) are considered an attractive target for cancer therapies. However, their origin remains controversial, with some evidence pointing at a local origin, whereas many publications suggest a significant contribution of progenitors from bone marrow. We found that TAFs derive almost exclusively from local sources. Therefore, therapeutic strategies to target fibroblasts must exploit local recruitment and the unique transcriptional and response patterns of fibroblasts from different sites.
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“The gradual nature of the transitions observed has given rise to the view that the majority of stromal fibroblasts initially originate from local fibroblasts that experience some form of tissue dysfunction31,32.”
From A framework for advancing our understanding of cancer-associated fibroblasts (2020) · cites this paper as [32]
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Metadata
- Authors
- Arina, A., Idel, C., Hyjek, E. M., Alegre, M.-L., Wang, Y., Bindokas, V. P., Weichselbaum, R. R., & Schreiber, H.
- Affiliations
- University of Chicago (US)
- Corresponding author
- Arina, Ainhoa
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2016-06-17
- Volume
- 113
- Issue
- 27
- Pages
- 7551-7556
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4941507
- OpenAlex
- W2442704894
- Cited by
- 238
- References
- 69
- Citations by year
- 2026: 20 · 2025: 38 · 2024: 35 · 2023: 37 · 2022: 26 · 2021: 29 · 2020: 21 · 2019: 12 · 2018: 12 · 2017: 7 · 2016: 1
- FWCI
- 5.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- HHS | National Institutes of Health (P01-CA97296, R01-CA22677, R01-CA37516)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- cancer-associated fibroblasts, tumor stroma, fibroblast origin, type I collagen, parabiosis, bone marrow chimeras, skin grafting, tumor microenvironment, collagen deposition
- MeSH terms
- Cancer-Associated Fibroblasts, Actins, Animals, Mice, Inbred C57BL, Neoplasms, Experimental, Mice, Knockout, Collagen Type I, Cell Line, Tumor, Green Fluorescent Proteins
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