Cited by 196Cancer, Hypoxia, and MetabolismCancer Cells and MetastasisImmune cells in cancer

Lactate is a mediator of metabolic cooperation between stromal carcinoma associated fibroblasts and glycolytic tumor cells in the tumor microenvironment

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Rattigan, Yanique I., Patel, Brijesh B., Ackerstaff, Ellen, Sukenick, George, Koutcher, Jason A., Glod, John W., Banerjee, Debabrata·2012·Experimental Cell Research

Abstract

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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  1. [42]Samuvel DJ Lactate boosts TLR4 signaling and NF-kappaB pathway-mediated gene transcription in macrophages via monocarboxylate transporters and MD-2 up-regulation J Immunol 182 4 2009 2476 2484 19201903 PMC2673542

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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)
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
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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