Adipose Tissue-Derived Stem Cells Differentiate into Carcinoma-Associated Fibroblast-Like Cells under the Influence of Tumor-Derived Factors
Open accessAbstract
Carcinoma-associated fibroblasts (CAF) are considered to contribute to tumor growth, invasion and metastasis. However, the cell type of origin remains unknown. Since human adipose tissue-derived stem cells (hASCs) are locally adjacent to breast cancer cells and might directly interact with tumor cells, we investigated whether CAFs may originate from hASCs. We demonstrated that a significant percentage of hASCs differentiated into a CAF-like myofibroblastic phenotype (e.g., expression of alpha smooth muscle actin and tenascin-C) when exposed to conditioned medium from the human breast cancer lines MDAMB231 and MCF7. The conditioned medium from MDAMB231 and MCF7 contains significant amounts of transforming growth factor-beta 1 (TGF β 1) and the differentiation of hASCs towards CAFs is dependent on TGF β 1 signaling via Smad3 in hASCs. The induction of CAFs can be abolished using a neutralizing antibody to TGF β 1 as well as by pretreatment of the hASCs with SB431542, a TGF β 1 receptor kinase inhibitor. Additionally, we found that these hASC-derived CAF-like cells exhibit functional properties of CAFs, including the ability to promote tumor cell invasion in an in vitro invasion assay, as well as increased expression of stromal-cell-derived factor 1 (SDF-1) and CCL5. Taken together, these data suggest that hASCs are a source of CAFs which play an important role in the tumor invasion.
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The use of MSCs themselves may contribute to tumor growth given reports of their predisposition to differentiate into cancer-associated fibroblasts, which are correlated with tumor growth, invasion and metastasis.
“The use of MSCs themselves may also have a contribution given the reports of their predisposition to differentiate into cancer-associated fibroblasts, which are correlated with tumor growth, invasion and metastasis [102], [103].”
From Mesenchymal stem cell secretome for regenerative medicine: Where do we stand? (2025) · cites this paper as [102]
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Self-citationBone-marrow-derived myofibroblasts contribute to the cancer-induced stromal reaction
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Role of tumor microenvironment in tumorigenesis
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- Authors
- Jotzu, C., Alt, E., Welte, G., Li, J., Hennessy, B. T., Devarajan, E., Krishnappa, S., Pinilla, S., Droll, L., & Song, Y.-H.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Corresponding author
- Song, Yao-Hua
- Venue
- Analytical Cellular Pathology
- Publisher
- Wiley
- Published
- 2010
- Volume
- 33
- Issue
- 2
- Pages
- 61-79
- ISSN
- 0921-8912 (ISSN-L)
- 2210-7177
- 2210-7185
- OpenAlex
- W4249372835
- Cited by
- 114
- References
- 5
- Citations by year
- 2026: 6 · 2025: 2 · 2024: 10 · 2023: 3 · 2022: 6 · 2021: 13 · 2020: 7 · 2019: 10 · 2018: 7 · 2017: 10 · 2016: 10 · 2015: 4 · 2014: 4 · 2013: 7 · 2012: 7
- FWCI
- 3.48
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Analytical Cellular Pathology (publishedVersion, cc-by)
- Funders
- U.S. Department of Defense (W81XWH-08-1-0523)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- adipose-derived stem cells, cancer-associated fibroblasts, breast cancer, tumor microenvironment, TGF-β1 signaling, Smad3, tumor invasion, myofibroblast differentiation, tumor-conditioned medium, CXCL12, RANTES
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