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

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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

DOI 10.1016/j.yexcr.2011.11.014PMC PMC3402174

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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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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
ORCID: Ackerstaff, Ellen
Koutcher, Jason A.
Glod, John W.
Banerjee, Debabrata
Venue: Experimental Cell Research
Publisher: Elsevier BV
Published: 2012-02
Volume: 318
Issue: 4
Pages: 326-335
ISSN: 0014-4827 (ISSN-L)
DOI: 10.1016/j.yexcr.2011.11.014
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
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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Lactate is a mediator of metabolic cooperation between stromal carcinoma associated fibroblasts and glycolytic tumor cells in the tumor microenvironment

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