Lactate and Pyruvate as Mediators of Metabolic Cooperation Between Stromal and Breast Cancer Cells

Ellen Ackerstaff¹, Brij B. Patel², Yanique I. Rattigan², Natalia Kruchevsky¹, John W. Glod², George Sukenick¹, Jason A. Koutcher¹, Debabrata Banerjee²

Previously, we have shown that cancer-associated fibroblasts (CAFs) take up and metabolize lactate. Here, we hypothesize that breast cancer cells and stromal cells have lactate-mediated metabolic coupling similar to muscle cells, where glycolytic muscle cells secrete lactate that is used by neighboring, oxidative muscle cells as an energy source. Our ¹³C MRS studies indicate that lactate-metabolizing CAFs secrete ¹³C-labeled pyruvate. While uptake of exogenous pyruvate in MDA-MB-231 breast cancer cells is increased by cocultured CAFs, subsequent ¹³C MRS indicates ¹³C-labeled lactate in the media conditioned by ¹³C-pyruvate-treated MDA-MB-231 cells, closing the cycle.