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

   


Authors: Rattigan, Y. I.; Patel, B. B.; Ackerstaff, E.; Sukenick, G.; Koutcher, J. A.; Glod, J. W.; Banerjee, D.
Article Title: Lactate is a mediator of metabolic cooperation between stromal carcinoma associated fibroblasts and glycolytic tumor cells in the tumor microenvironment
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 13C NMR spectroscopic measurements indicate that 13C-lactate is converted to 13C-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. © 2011 Elsevier Inc.
Keywords: glycolytic tumor cells; lactate metabolism; stromal carcinoma-associated fibroblasts (cafs)
Journal Title: Experimental Cell Research
Volume: 318
Issue: 4
ISSN: 0014-4827
Publisher: Elsevier Inc.  
Date Published: 2012-02-15
Start Page: 326
End Page: 335
Language: English
DOI: 10.1016/j.yexcr.2011.11.014
PROVIDER: scopus
PUBMED: 22178238
PMCID: PMC3402174
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-84856103868&partnerID=40&md5=10201efebef023d73e5f956bbc7c2d35
Notes: --- - "Export Date: 1 March 2012" - "CODEN: ECREA" - "Source: Scopus"
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MSK Authors
  1. Jason A Koutcher
    278 Koutcher
  2. George D Sukenick
    23 Sukenick
  3. Ellen Ackerstaff
    43 Ackerstaff
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