Lactate-Mediated Metabolic Cooperation between Human Stromal & Breast Cancer Cells

Ellen Ackerstaff¹, Brijesh B. Patel², Yanique I. Rattigan², George Sukenick³, Natalia Kruchevsky¹, John W. Glod², Jason A. Koutcher¹, Debabrata Banerjee²

We hypothesize that tumor cells recruit stromal cells and that stromal cells metabolize lactate expelled by tumor cells into the microenvironment. Human mesenchymal stem cells (hMSCs) are bone marrow-derived stromal cells which migrate toward hypoxic tumor cells and overexpress functional monocarboxylate transporter 1 in response to lactate exposure. Naive hMSCs and carcinoma-associated fibroblasts (CAFs) exposed to ¹³C-3-lactate, produced detectable levels of ¹³C-α-ketoglutarate. Additional ¹⁴C-lactate studies showed that lactate uptake in CAFs was higher than in hMSCs. Also, lactate stimulated hMSC migration. Our results suggests the metabolic cooperation between stromal and tumor cells.