Glycolysis as Primary Energy Source in Tumor Cell Chemotaxis

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Abstract
The energy requirements via glycolytic pathways were directly measured in migrating tumor cells. Motility in the metastatic human melanoma cell line A2058, stimulated by insulinlike growth factor I (IGF–I), depends on glycolysis in the presence of glucose as its principal source of energy. Motility in glucose–free medium was 75% reduced and utilized mitochondrial respiration (inhibited by oligomycin). With increasing (physiologic) glucose concentrations, there was a dramatic shift to anaerobic glycolysis as the energy source and 93% elimination of the oligomycin inhibition of motility. Oxamate, an inhibitor of glycolysis, inhibited motility at all glucose concentrations. CO 2 production from glycolysis and from the hexose monophosphate shunt was measured in migrating tumor cells. The time course and glucose–dosedependence of glycolytic CO 2 production correlated directly with motility. In contrast, mitochondrial CO 2 production was inversely related to glucose concentration. A monoclonal antibody for the IGF–I receptor inhibited both motility and glycolytic CO 2 production, indicating that both processes are receptor mediated. [J Natl Cancer Inst 82:1836–1840, 1990]