Fig. 4.

Model depicting metabolic commensalism of oxidative cancer cells for stromal cells. In the model, oxidative cancer cells, depicted on the right, produce reactive oxygen species (ROS) that promote glycolysis and MCT4 expression in stromal cells. Glycolytic stromal cells, depicted on the left, import glucose via glucose transporters (GLUT) and then sequentially convert glucose to pyruvate and ATP using glycolysis, and pyruvate to lactate using lactate dehydrogenase A (LDHA). They also produce ketone bodies. Lactate and ketone bodies are exported together with protons via MCT4. Oxidative cancer cells import lactate, ketone bodies and protons via MCT1. Lactate is oxidized to pyruvate by lactate dehydrogenase B (LDHB) generating NADH as a byproduct, and both pyruvate and NADH fuel the TCA cycle to support ATP production through oxidative phosphorylation. Ketone bodies can also be catabolized.