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(PP021) Lactate consumption by the rat R3230 mammary adenocarcinoma.
Richardson, Rachel*,1, Gamcsik, Michael2, Biaglow, John3, Dewhirst, Mark, 1 Radiation Oncology, Durham, NC, USA2 Medicine, Durham, NC, USA3 Radiation Oncology, Philadelphia, PA, USA
ABSTRACT- Many tumor types have been shown to have high glycolytic rates resulting in high lactate levels and decreased pH in tumors. Lactate is usually thought of as an end-product of glycolysis that is transported out of tumor cells to be recycled by other tissues including: liver, heart, and skeletal muscle. However, recent evidence suggests lactate can be consumed by tumor cells, most likely for energy production. We demonstrate that the R3230 rat mammary adenocarcinoma consumes 13C-labeled lactate in vivo using 13C-NMR spectroscopy. Additionally, we show that the lactate is converted into alanine and glutamate, both in vivo and in vitro. This is one of the first studies to demonstrate lactate is consumed by tumor cells and it is the first to show that this consumption results in alanine production. The R3230 tumor also has been shown to avidly take up glucose and produce lactate. Based on this combined data we hypothesize there may be a symbiotic relationship between different cells in the same tumor. Consequently, some tumor cells may consume glucose and produce lactate, which other cells can utilize. Alanine is a substrate for G-protein production and for porphyrin synthesis, both of which could provide tumor cells with growth advantage. If the metabolic interaction occurs between lactate producing and lactate consuming cells, it could provide a significant survival advantage for those tumor cells that are less well oxygenated. This work was supported by grants from the NIH CA40355 and add your grant.
Key words: lactate, metabolism, tumor, glucose
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