The potential role of transformation-induced metabolic changes in tumor-host interaction.
Increased glycolysis in transformed cell coupled with increased membrane Na+/H+ exchange produces significant environmental fluctuations in and around tumors, including enhanced local glucose consumption and based competition model that examines the effects of these environmental changes on tumor-host interaction. By generating a critical parameter (J) for each population at the tumor-host interface, the interactive dynamics can be predicted. Although necessarily limited by simplifying assumptions, the model demonstrates that the metabolic changes of transformation and their environmental consequences could confer significant advantages on tumor populations by decreasing their J value and, through the generation of glucose and pH gradients, increasing the J value of adjacent normal cells. Thus, the well-documented metabolic changes associated with transformation, including increased glycolysis, glucose utilization, and lactic acid production with reversal of the normal intracellular-extracellular pH gradient, phenomena now consistently demonstrated in human tumors in situ, provide a potential mechanism of tumor invasion that is simple, complete, and sufficiently general to apply to many classes of tumors. The model explicitly predicts that in situ measurement of tumor glucose utilization and H+ production will determine prognosis. Furthermore, it predicts therapies that chronically reduce tumor glucose utilization and/or H+ production or increase the buffering capacity in normal tissue will be effective in tumor prevention and tumor treatment.
Gatenby
R A
RA
Fels Institute for Molecular Biology, Temple University Hospitial, Philadelphia, Pennsylvania 19140, USA.
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008433:Mathematics; D008954:Models, Biological; D017923:Sodium-Hydrogen Exchangers / Q000502:physiology
D017923:Sodium-Hydrogen Exchangers; D005947:Glucose