Interleukin 6 secreted from adipose stromal cells promotes migration and invasion of breast cancer cells
Open accessAbstract
Excessive adiposity has long been associated with increased incidence of breast cancer in post-menopausal women, and with increased mortality from breast cancer, regardless of the menopausal status. Although adipose tissue-derived estrogen contributes to obesity-associated risk for estrogen receptor (ER)-positive breast cancer, the estrogen-independent impact of adipose tissue on tumor invasion and progression needs to be elucidated. Here, we show that adipose stromal cells (ASCs) significantly stimulate migration and invasion of ER-negative breast cancer cells in vitro and tumor invasion in a co-transplant xenograft mouse model. Our study also identifies cofilin-1, a known regulator of actin dynamics, as a determinant of the tumor-promoting activity of ASCs. The cofilin-1-dependent pathway affects the production of interleukin 6 (IL-6) in ASCs. Depletion of IL-6 from the ASC-conditioned medium abrogated the stimulatory effect of ASCs on the migration and invasion of breast tumor cells. Thus, our study uncovers a link between a cytoskeleton-based pathway in ASCs and the stromal impact on breast cancer cells.
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Bone marrow-derived MSC and adipose-derived stem/stromal cells can also enhance cancer cell migration, invasion and metastasis through release of IL-6 in the tumor microenvironment.
“BM-MSC and ASC could also potentiate cancer cell migration, invasion and metastasis via the release of IL-6 in the tumor microenvironment [116, 120].”
From Mesenchymal stem cell secretome and regenerative therapy after cancer (2013) · cites this paper as [116]
The Results section reports that depleting IL-6 from ASC-conditioned medium reduced breast cancer cell migration and invasion. The paper does not establish that ASC-derived IL-6 promotes metastasis; its Discussion describes IL-6-associated metastasis in bone marrow as a finding from another study. No page numbers are available in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredElevated 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 [116]
The Results report IL-6 secretion by adipose stromal cells and its role in breast cancer cell migration and invasion. The Discussion says the stromal cells came from cancer-free donors and had not been exposed to a tumor environment. The paper therefore does not establish that interaction with malignant cells elevated IL-6 secretion, or document that effect across epithelial, hematopoietic and mesenchymal cancers. Page numbers were not available in our copy. (LLM, conf=0.86)
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References 50 · Cited by 312
- Authors
- Walter, M., Liang, S., Ghosh, S., Hornsby, P. J., & Li, R.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- Corresponding author
- Li, R
- ORCID
- Ghosh, S
- Venue
- Oncogene
- Published
- 2009-06-01
- Volume
- 28
- Issue
- 30
- Pages
- 2745-2755
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- PMC
- PMC2806057
- OpenAlex
- W1973452897
- Cited by
- 312
- References
- 50
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 14 · 2023: 13 · 2022: 24 · 2021: 28 · 2020: 21 · 2019: 22 · 2018: 26 · 2017: 22 · 2016: 19 · 2015: 17 · 2014: 18 · 2013: 19 · 2012: 18
- FWCI
- 11.64
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Site cant be reached (submittedVersion)
- Funders
- Glenn Foundation for Medical Research
- National Cancer Institute (R01CA093506, CA93506)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Oncology › Cancer Risks and Factors
- Keywords
- interleukin-6, adipose stromal cells, breast cancer, tumor cell migration, tumor invasion, cofilin-1, actin cytoskeleton, tumor microenvironment, obesity, estrogen receptor-negative breast cancer, stromal-epithelial interactions, conditioned medium
- MeSH terms
- Animals, Breast Neoplasms, Cell Movement, Female, Humans, Male, Neoplasm Invasiveness, Neoplasm Transplantation, Transplantation, Heterologous, Interleukin-6, Stromal Cells, Adipocytes, Cell Line, Tumor, Cofilin 1, Mice, rho-Associated Kinases
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