The DOI matches its Crossref record; 45 of the 46 references it cites were found in a registry or an index.
Lactate is a mediator of metabolic cooperation between stromal carcinoma associated fibroblasts and glycolytic tumor cells in the tumor microenvironment
Open accessAbstract
Human mesenchymal stem cells (hMSCs) are bone marrow-derived stromal cells, which play a role in tumor progression. We have shown earlier that breast cancer cells secrete higher levels of interleukin-6 (IL-6) under hypoxia, leading to the recruitment of hMSCs towards hypoxic tumor cells. We found that (i) MDA-MB-231 cells secrete significantly higher levels of lactate (3-fold more) under hypoxia (1% O(2)) than under 20% O(2) and (ii) lactate recruits hMSCs towards tumor cells by activating signaling pathways to enhance migration. The mRNA and protein expression of functional MCT1 in hMSCs is increased in response to lactate exposure. Thus, we hypothesized that hMSCs and stromal carcinoma associated fibroblasts (CAFs) in the tumor microenvironment have the capacity to take up lactate expelled from tumor cells and use it as a source of energy. Our (13)C NMR spectroscopic measurements indicate that (13)C-lactate is converted to (13)C-alpha ketoglutarate in hMSCs and CAFs supporting this hypothesis. To our knowledge this is the first in vitro model system demonstrating that hMSCs and CAFs can utilize lactate produced by tumor cells.
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“Recent findings implicate TME in the induced metabolic rewiring in cancer cells (Cairns et al., 2011; Fiaschi and Chiarugi, 2012; Rattigan et al., 2012).”
From Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism (2016) · cites this paper as Rattigan et al., 2012
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Accessories to the Crime: Functions of Cells Recruited to the Tumor Microenvironment
Hanahan, D., & Coussens, L. M. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.02.022 · Cited by 4,632
Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism
Zhao, H., Yang, L., Baddour, J., Achreja, A., Bernard, V., Moss, T., Marini, J. C., Tudawe, T., Seviour, E. G., San Lucas, F. A., et al. (2016) · eLife · doi:10.7554/elife.10250 · Cited by 927
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“For example, breast and colon cancer cells consume glucose and release lactate to surrounding fibroblasts and mesenchymal stem cells [56, 57] (Fig.”
BackgroundHusain, Z., Huang, Y., Seth, P., & Sukhatme, V. P. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1202702 · Cited by 827
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Metadata
- Authors
- Rattigan, Y. I., Patel, B. B., Ackerstaff, E., Sukenick, G., Koutcher, J. A., Glod, J. W., & Banerjee, D.
- Affiliations
- Rutgers Cancer Institute (US)
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Banerjee, Debabrata
- Venue
- Experimental Cell Research
- Publisher
- Elsevier BV
- Published
- 2012-02
- Volume
- 318
- Issue
- 4
- Pages
- 326-335
- ISSN
- 0014-4827 (ISSN-L)
- PMC
- PMC3402174
- OpenAlex
- W2106506721
- Cited by
- 196
- References
- 46
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 27 · 2023: 16 · 2022: 13 · 2021: 15 · 2020: 20 · 2019: 10 · 2018: 9 · 2017: 16 · 2016: 11 · 2015: 15 · 2014: 12 · 2013: 9 · 2012: 6
- FWCI
- 2.94
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Experimental Cell Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (CA83084, P01 CA94060)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- lactate, metabolic cooperation, human mesenchymal stem cells, tumor microenvironment, hypoxia, breast cancer, MDA-MB-231 cells, lactate transport, MCT1, alpha-ketoglutarate, interleukin-6, cell migration, 13C NMR
- MeSH terms
- Hypoxia, Breast Neoplasms, Carcinoma, Cell Communication, Female, Fibroblasts, Glycolysis, Humans, Stromal Cells, Lactic Acid, Paracrine Communication, Cell Line, Tumor, Metabolic Networks and Pathways, Tumor Microenvironment, Mesenchymal Stem Cells
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