Tissue-resident stem cells promote breast cancer growth and metastasis
Open accessAbstract
Mesenchymal stem cells derived from bone marrow have recently been described to localize to breast carcinomas and to integrate into the tumor-associated stroma. In the present study, we investigated whether adipose tissue-derived stem cells (ASCs) could play a role in tumor growth and invasion. Compared with bone marrow-derived cells, ASCs as tissue-resident stem cells are locally adjacent to breast cancer cells and may interact with tumor cells directly. Here, we demonstrate that ASCs cause the cancer to grow significantly faster when added to a murine breast cancer 4T1 cell line. We further show that breast cancer cells enhance the secretion of stromal cell-derived factor-1 from ASCs, which then acts in a paracrine fashion on the cancer cells to enhance their motility, invasion and metastasis. The tumor-promoting effect of ASCs was abolished by knockdown of the chemokine C-X-C receptor 4 in 4T1 tumor cells. We demonstrated that ASCs home to tumor site and promote tumor growth not only when co-injected locally but also when injected intravenously. Furthermore, we demonstrated that ASCs incorporate into tumor vessels and differentiate into endothelial cells. The tumor-promoting effect of tissue-resident stem cells was also tested and validated using a human breast cancer line MDA-MB-231 cells and human adipose tissue-derived stem cells. Our findings indicate that the interaction of local tissue-resident stem cells with tumor stem cells plays an important role in tumor growth and metastasis.
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CCL5, also called RANTES, is another MSC-secreted pro-metastasis cytokine that can be secreted upon interaction with cancer cells and is associated with tumor progression and invasion in various cancers.
“Another MSC-secreted pro-metastasis cytokine, CCL5 (RANTES), can be secreted upon interaction with cancer cells and is associated with tumor progression and invasion in various cancers [73, 87, 100, 142–144].”
From Mesenchymal stem cell secretome and regenerative therapy after cancer (2013) · cites this paper as [73]
The tumor-growth section reports that adipose-derived stem cells produced RANTES when exposed to breast cancer cells, and the Discussion reports that RANTES enhances breast cancer cell invasion and metastasis. The passages do not establish an association between RANTES and tumor progression and invasion across various cancers; they address breast cancer. (LLM, conf=0.86)
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- Authors
- Muehlberg, F. L., Song, Y.-H., Krohn, A., Pinilla, S. P., Droll, L. H., Leng, X., Seidensticker, M., Ricke, J., Altman, A. M., Devarajan, E., Liu, W., Arlinghaus, R. B., & Alt, E. U.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- University Hospital Magdeburg (DE)
- Corresponding author
- Alt, Eckhard U.
- ORCID
- Venue
- Carcinogenesis
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-01-30
- Volume
- 30
- Issue
- 4
- Pages
- 589-597
- ISSN
- 0143-3334 (ISSN-L)
- 1460-2180
- OpenAlex
- W2107402669
- Cited by
- 330
- References
- 71
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 13 · 2023: 9 · 2022: 11 · 2021: 19 · 2020: 10 · 2019: 17 · 2018: 18 · 2017: 13 · 2016: 20 · 2015: 33 · 2014: 35 · 2013: 24 · 2012: 31
- FWCI
- 16.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Carcinogenesis (publishedVersion)
- PubMed (publishedVersion)
- BORIS (University Library Bern) (submittedVersion, other-oa)
- Open Access CRIS of the University of Bern
- Funders
- U.S. Department of Defense (W81XWH, W81XWH0810523)
- 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 › Angiogenesis and VEGF in Cancer
- Keywords
- tissue-resident stem cells, adipose-derived stem cells, breast cancer, tumor growth, metastasis, CXCL12, CXCR4, paracrine signaling, tumor cell motility, tumor invasion, stem cell homing, tumor vasculature, endothelial differentiation, tumor microenvironment, 4T1 cells, MDA-MB-231 cells
- MeSH terms
- Adipose Tissue, Animals, Cell Movement, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Lung Neoplasms, Male, Mice, Inbred BALB C, Mice, Nude, Neoplasm Invasiveness, Neovascularization, Pathologic, Neoplastic Stem Cells, Blotting, Western, Mammary Neoplasms, Animal, Stromal Cells, Spheroids, Cellular, Receptors, CXCR4, Vascular Endothelial Growth Factor A, Immunoprecipitation, Mice, Chemokine CXCL12
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