Glioma Neuron Symbiosis: A Hypothesis

For their energy needs, cancer cells require large amounts of glucose, since they use the inefficient glycolytic pathway (Warburg effect), producing only two moles of lactate and two moles of adenosine triphosphate for each mole of glucose consumed. By contrast, normal cells consume glucose via glycolysis and utilize its end-product, lactate, as the substrate of the oxidative mitochondrial tricarboxylic acid cycle and it’s coupled oxidative phosphorylation. This process is 18 times more efficient in producing adenosine triphosphate than glycolysis alone. It is hypothesized here that lactate, produced by cancer cells, is preferentially used oxidatively by normal cells surrounding those cancer cells, bypassing glycolysis and sparing glucose, which is readily available for the glucose-craving cancer cells. Moreover, especially where gliomas are concerned, their ability to secrete glutamate, which excites glutamatergic neurons, drives the latter to consume even more lactate and spare more glucose. Such symbiotic exchange, especially at the early stages of malignancy, assures the budding cancer cells an ample glucose supply ahead of the development of additional vasculature. This hypothesis focuses on brain cancers but may also apply to other cancer types.