Bone marrow contribution to tumor-associated myofibroblasts and fibroblasts
Open accessAbstract
The role of myofibroblasts in tissue repair and fibrosis is well documented, but the source of these myofibroblasts is unclear. There is evidence of a circulating population of fibrocytes that can home to areas of injury and contribute to myofibroblast populations. Previously, we have shown that the bone marrow is a source of myofibroblasts for many tissues including the gut, lung, and kidney and that this phenomenon is exacerbated by injury. We now show that the bone marrow can contribute to myofibroblast and fibroblast populations in tumor stroma in a mouse model of pancreatic insulinoma. Mice transgenic for the rat insulin promoter II gene linked to the large-T antigen of SV40 (RIPTag) develop solid β-cell tumors of the pancreas. Approximately 25% of myofibroblasts in these pancreatic tumors were donor-derived, and these were concentrated toward the edge of the tumor. Thus, the development of tumor stroma is at least in part a systemic response that may ultimately yield methods of targeting new therapy.
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Once in the tumor microenvironment, MSC can enhance tumorigenesis by differentiating into tumor-nurturing stroma such as tumor-associated fibroblasts and myofibroblasts, by direct cell contact with cancer cells, or by releasing paracrine factors.
“There they can potentiate further tumorigenesis via differentiation into tumor-nurturing stroma (TAF, myofibroblasts) [82, 104], direct cell contact interaction with cancer cells [105, 106] or release of paracrine factors (Table 2).”
From Mesenchymal stem cell secretome and regenerative therapy after cancer (2013) · cites this paper as [104]
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- Authors
- Direkze, N. C., Hodivala-Dilke, K., Jeffery, R., Hunt, T., Poulsom, R., Oukrif, D., Alison, M. R., & Wright, N. A.
- Affiliations
- Cancer Research UK (GB)
- 1Cancer Research UK;
- University College London (GB)
- Queen Mary University of London (GB)
- Venue
- Cancer Research
- Published
- 2004-12-01
- Volume
- 64
- Issue
- 23
- Pages
- 8492-8495
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W1965691956
- Cited by
- 530
- References
- 20
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 16 · 2023: 16 · 2022: 19 · 2021: 22 · 2020: 29 · 2019: 18 · 2018: 21 · 2017: 17 · 2016: 23 · 2015: 21 · 2014: 34 · 2013: 37 · 2012: 37
- FWCI
- 11.36
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- myofibroblasts, fibroblasts, bone marrow, tumor stroma, pancreatic insulinoma, fibroblast origin, tissue repair, fibrosis, beta cell tumors, donor-derived cells, tumor microenvironment
- MeSH terms
- Actins, Animals, Bone Marrow Cells, Female, Fibroblasts, Immunohistochemistry, Insulinoma, Male, Mice, Transgenic, Muscle, Smooth, Pancreatic Neoplasms, Bone Marrow Transplantation, In Situ Hybridization, Green Fluorescent Proteins, Mice
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