Ketones Fuel Cancer?!

Ketones and lactate “fuel” tumor growth and metastasis

Previously, we proposed a new model for understanding the “Warburg effect” in tumor metabolism. In this scheme, cancer-associated fibroblasts undergo aerobic glycolysis and the resulting energy-rich metabolites are then transferred to epithelial cancer cells, where they enter the TCA cycle, resulting in high ATP production via oxidative phosphorylation. We have termed this new paradigm “the Reverse Warburg effect.” 

Here, we directly evaluate whether the end-products of aerobic glycolysis (3-hydroxy-butyrate and L-lactate) can stimulate tumor growth and metastasis, using MDA-MB-231 breast cancer xenografts as a model system. More specifically, we show that administration of 3-hydroxy-butyrate (a ketone body) increases tumor growth by ~2.5-fold, without any measurable increases in tumor vascularization/angiogenesis. Both 3-hydroxy-butyrate and L-lactate functioned as chemo-attractants, stimulating the migration of epithelial cancer cells.  Although L-lactate did not increase primary tumor growth, it stimulated the formation of lung metastases by ~10-fold.  thus, we conclude that ketones and lactate fuel tumor growth and metastasis, providing functional evidence to support the “reverse Warburg effect.” 

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