Ketones and lactate “fuel” tumor growth and metastasis

• DOI: 10.4161/cc.9.17.12731
• Publication Date: 2010-09-17T20:33:15Z
• Authors: Gloria Bonuccelli; Aristotelis Tsirigos; Diana Whitaker-Me...; Stephanos Pavlides; Richard G. Pestell; Barbara Chiavarina; Philippe G. Frank; Neal Flomenberg; Anthony Howell; Ubaldo E. Martine...; Federica Sotgia; Michael P. Lisanti
• Keywords: Warburg Effect; Anaerobic glycolysis

Previously, we proposed a new model for understanding the "Warburg effect" in tumor metabolism. In this scheme, cancer-associated fibroblasts undergo aerobic glycolysis and resulting energy-rich metabolites are then transferred to epithelial cancer cells, where they enter TCA cycle, high ATP production via oxidative phosphorylation. We have termed paradigm "The Reverse Warburg Effect." Here, directly evaluate whether end-products of (3-hydroxy-butyrate L-lactate) can stimulate growth metastasis, using MDA-MB-231 breast xenografts as system. More specifically, show that administration 3-hydroxy-butyrate (a ketone body) increases by ~2.5-fold, without any measurable vascularization/angiogenesis. Both L-lactate functioned chemo-attractants, stimulating migration cells. Although did not increase primary growth, it stimulated formation lung metastases ~10-fold. Thus, conclude ketones lactate fuel providing functional evidence support "Reverse Moreover, discuss possibility may be unwise use lactate-containing i.v. solutions (such Lactated Ringer's or Hartmann's solution) patients, given dramatic metastasis-promoting properties L-lactate. Also, provide up-regulation mitochondrial metabolism cycle human cells vivo, an informatics analysis existing raw transcriptional profiles adjacent stromal Lastly, our findings explain why diabetic patients increased incidence cancer, due production, tendency towards autophagy/mitophagy their adipose tissue.