Carcinoma-associated fibroblast-like differentiation of human mesenchymal stem cells
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Abstract
Carcinoma-associated fibroblasts (CAF) have recently been implicated in important aspects of epithelial solid tumor biology, such as neoplastic progression, tumor growth, angiogenesis, and metastasis. However, neither the source of CAFs nor the differences between CAFs and fibroblasts from nonneoplastic tissue have been well defined. In this study, we show that human bone marrow–derived mesenchymal stem cells (hMSCs) exposed to tumor-conditioned medium (TCM) over a prolonged period of time assume a CAF-like myofibroblastic phenotype. More importantly, these cells exhibit functional properties of CAFs, including sustained expression of stromal-derived factor-1 (SDF-1) and the ability to promote tumor cell growth both in vitro and in an in vivo coimplantation model, and expression of myofibroblast markers, including α-smooth muscle actin and fibroblast surface protein. hMSCs induced to differentiate to a myofibroblast-like phenotype using 5-azacytidine do not promote tumor cell growth as efficiently as hMSCs cultured in TCM nor do they show increased SDF-1 expression. Furthermore, gene expression profiling revealed similarities between TCM-exposed hMSCs and CAFs. Taken together, these data suggest that hMSCs are a source of CAFs and can be used in the modeling of tumor-stroma interactions. To our knowledge, this is the first report showing that hMSCs become activated and resemble carcinoma-associated myofibroblasts on prolonged exposure to conditioned medium from MDAMB231 human breast cancer cells. [Cancer Res 2008;68(11):4331–9]
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MSC can be mobilized and recruited to active tumor sites, where they can become part of the tumor microenvironment.
“MSC can be mobilized and recruited to active tumor sites, where they can incorporate into the tumor’s microenvironment [5, 68, 100–103].”
From Mesenchymal stem cell secretome and regenerative therapy after cancer (2013) · cites this paper as [102]
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- Authors
- Mishra, P. J., Mishra, P. J., Humeniuk, R., Medina, D. J., Alexe, G., Mesirov, J. P., Ganesan, S., Glod, J. W., & Banerjee, D.
- Affiliations
- 1Medicine, Departments of
- Broad Institute (US)
- Rutgers Cancer Institute (US)
- Venue
- Cancer Research
- Published
- 2008-06-01
- Volume
- 68
- Issue
- 11
- Pages
- 4331-4339
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- PMC
- PMC2725025
- OpenAlex
- W2161214210
- Cited by
- 912
- References
- 38
- Citations by year
- 2026: 14 · 2025: 28 · 2024: 45 · 2023: 37 · 2022: 49 · 2021: 63 · 2020: 76 · 2019: 46 · 2018: 42 · 2017: 38 · 2016: 52 · 2015: 60 · 2014: 53 · 2013: 77 · 2012: 65
- FWCI
- 29.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Rutgers Cancer Institute of New Jersey
- National Cancer Institute (R01CA121941)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- cancer-associated fibroblasts, mesenchymal stem cells, tumor-conditioned medium, myofibroblast differentiation, CXCL12, tumor-stroma interactions, breast cancer, MDA-MB-231 cells, alpha-smooth muscle actin, azacitidine, tumor microenvironment
- MeSH terms
- Animals, Base Sequence, Cell Differentiation, Cell Division, Fibroblasts, Fluorescent Antibody Technique, Humans, Mice, Nude, Neoplasms, Culture Media, Conditioned, DNA Primers, Reverse Transcriptase Polymerase Chain Reaction, Cell Line, Tumor, Mice, Mesenchymal Stem Cells
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