Ellen Ackerstaff1, Brijesh B. Patel2, Yanique I. Rattigan2, George Sukenick3, Natalia Kruchevsky1, John W. Glod2, Jason A. Koutcher1, Debabrata Banerjee2
1Memorial Sloan-Kettering Cancer Center, New York, NY, USA; 2The Cancer Institute of New Jersey, RWJMS, UMDNJ, New Brunswick, NJ, USA; 3Sloan-Kettering Institute, New York, NY, USA
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.