Scientists have discovered that lactate provides a fuel for growing tumors, challenging a nearly century-old observation known as the Warburg effect.

"We were completely shocked by our findings," said the senior author. "The oldest observation in cancer metabolism, the Warburg effect, says that lactate is a waste product of the tumor. This concept has driven the vast amount of research in the field. Our finding is a fundamental change in how we think about tumor metabolism."

The Warburg effect, named after the German cancer biologist Otto Warburg, has three main components:

• Rapid glucose uptake.

• Reduced glucose oxidation even when oxygen is present.

• Secretion of lactate as a waste product.

In the study published in Cell, the researchers showed lactate is not only a waste product but also acts as a fuel source consumed by lung cancer cells growing in patients and mice. Combined with a previous study, also published in Cell, that showed activated glucose oxidation in tumors, the results of this study are challenging the tenets of the Warburg effect.

Infusing human lung cancer patients with 13C-lactate revealed extensive labeling of TCA cycle metabolites. In mice, deleting monocarboxylate transporter-1 (MCT1) from tumor cells eliminated lactate-dependent metabolite labeling, confirming tumor-cell-autonomous lactate uptake.

Strikingly, directly comparing lactate and glucose metabolism in vivo indicated that lactate’s contribution to the TCA cycle predominates.

"We believe that lactate is one of the fuels that supports growth, proliferation, and maybe even lung cancer metastases," senior author said. "Cancer metabolism is clinically actionable, and understanding the lactate pathway could help us find therapeutic targets for lung cancer. Lactate uptake could also have predictive value when used as an imaging tracer."
Additional findings in the study suggest a potential link between lactate use and cancer aggression.

"The findings are preliminary, but we did see a connection between lactate utilization and how quickly the tumors metastasized or recurred. This result suggests that there is something fundamental about the lactate utilization pathway that pertains to the clinical aggressiveness of the tumor," said the lead author of the study.

http://www.utsouthwestern.edu/newsroom/articles/year-2017/cri-lactate-deberardinis.html

http://www.cell.com/cell/fulltext/S0092-8674(17)31068-1