Dynamic Metabolic Signatures of Metastatic and Non-Metastatic Breast Cancer Cells

Rui Vasco Simoes¹, Ellen Ackerstaff¹, Natalia Kruchevsky¹, Yang Pu, ¹², George Sukenick¹, Jason A. Koutcher¹

Distinguishing non-invasively metastatic from non-metastatic clinical breast cancer, would significantly improve evaluation of patients prognoses. Two isogenic murine breast cancer lines, metastatic 4T1 and non-metastatic 67NR, were studied in an NMR-compatible cell perfusion system to investigate their dynamic metabolic responses to (a) oxygen availability vs. hypoxia, and (b) glutamine supply vs. deprivation. When exposed to these stress conditions, each cell line adopted different metabolic strategies. Non-metastatic 67NR cells revealed overall higher glycolytic activity than metastatic 4T1 cells. In the more aggressive cell line, glycolysis is glutamine-dependent during hypoxia, and decreases when oxygen becomes available to favor TCA cycle activity.