Breast cancer stem cells are regulated by mesenchymal stem cells through cytokine networks
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Abstract
We have used in vitro and mouse xenograft models to examine the interaction between breast cancer stem cells (CSC) and bone marrow–derived mesenchymal stem cells (MSC). We show that both of these cell populations are organized in a cellular hierarchy in which primitive aldehyde dehydrogenase expressing mesenchymal cells regulate breast CSCs through cytokine loops involving IL6 and CXCL7. In NOD/SCID mice, labeled MSCs introduced into the tibia traffic to sites of growing breast tumor xenografts where they accelerated tumor growth by increasing the breast CSC population. With immunochemistry, we identified MSC–CSC niches in these tumor xenografts as well as in frozen sections from primary human breast cancers. Bone marrow–derived MSCs may accelerate human breast tumor growth by generating cytokine networks that regulate the CSC population. Cancer Res; 71(2); 614–24. ©2011 AACR.
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Elevated IL-6 secretion by MSC has been detected after interaction with malignant cells in several epithelial, hematopoietic and mesenchymal cancers.
“Secretion of elevated levels of IL-6 by MSC has been detected upon interaction with malignant cells in several epithelial, hematopoietic and mesenchymal cancers (Table 2) [43, 69, 76, 77, 82, 115–119].”
From Mesenchymal stem cell secretome and regenerative therapy after cancer (2013) · cites this paper as [115]
The Results section on the cytokine network reports increased IL-6 gene expression in both mesenchymal and breast cancer cells after co-culture, along with increased IL-6 protein in the co-culture. It does not establish that the extra secreted protein came specifically from MSCs, or examine interactions across hematopoietic and mesenchymal cancers. The broader cancer-type claim is therefore unsupported by this paper. (LLM, conf=0.86)
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Research works printed but not linked: 2
- [16]Charafe-Jauffret E Ginestier C Iovino F Breast cancer cell lines contain functional cancer stem cells with metastatic capacity and a distinct molecular signature Cancer Res 2009 69 1302 13 19190339 PMC2819227
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- Authors
- Liu, S., Ginestier, C., Ou, S. J., Clouthier, S. G., Patel, S. H., Monville, F., Korkaya, H., Heath, A., Dutcher, J., Kleer, C. G., Jung, Y., Dontu, G., Taichman, R., & Wicha, M. S.
- Affiliations
- Inserm (FR)
- Authors' Affiliations: 1Comprehensive Cancer Center and 2School of Dentistry, University of Michigan, Ann Arbor, Michigan; and 3Centre de Recherche en Cancerologie de Marseille, Laboratoire d'Oncologie Moleculaire, UMR891 Inserm/Institut Paoli-Calmettes, Marseille, France
- Corresponding author
- Liu, Suling
- ORCID
- Venue
- Cancer Research
- Published
- 2011-01-13
- Volume
- 71
- Issue
- 2
- Pages
- 614-624
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- PMC
- PMC3100554
- OpenAlex
- W2142112207
- Cited by
- 611
- References
- 33
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 23 · 2023: 24 · 2022: 29 · 2021: 34 · 2020: 29 · 2019: 50 · 2018: 44 · 2017: 40 · 2016: 58 · 2015: 58 · 2014: 64 · 2013: 60 · 2012: 46
- FWCI
- 32.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- University of Michigan
- National Cancer Institute (CA101860, R01CA129765, CA129765, U01CA154224, R01CA125577, R01CA101860, P30CA046592, R01CA107469)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- breast cancer stem cells, mesenchymal stem cells, bone marrow-derived stem cells, cytokine network, interleukin-6, CXCL7, aldehyde dehydrogenase, tumor microenvironment, tumor growth, stem cell niche, xenograft models, NOD/SCID mice
- MeSH terms
- Aldehyde Dehydrogenase, Animals, Bone Marrow Cells, Breast Neoplasms, Cell Communication, Female, Humans, Transplantation, Heterologous, Neoplastic Stem Cells, Cytokines, Mice, SCID, Mice, Inbred NOD, Mice, Mesenchymal Stem Cells
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