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

Exp Cell Res. 2012 Feb 15;318(4):326-35. doi: 10.1016/j.yexcr.2011.11.014. Epub 2011 Dec 8.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Carcinoma / metabolism*
  • Carcinoma / pathology
  • Cell Communication / drug effects
  • Cell Communication / physiology
  • Cell Line, Tumor
  • Female
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Fibroblasts / physiology
  • Glycolysis / drug effects*
  • Glycolysis / physiology
  • Humans
  • Hypoxia / metabolism
  • Hypoxia / pathology
  • Lactic Acid / pharmacology*
  • Mesenchymal Stem Cells / metabolism
  • Mesenchymal Stem Cells / pathology
  • Metabolic Networks and Pathways / drug effects*
  • Paracrine Communication / drug effects
  • Paracrine Communication / physiology
  • Stromal Cells / drug effects*
  • Stromal Cells / metabolism
  • Stromal Cells / pathology
  • Tumor Microenvironment / drug effects*
  • Tumor Microenvironment / physiology


  • Lactic Acid