THE POTENTIAL ROLE OF TRANSFORMATION-INDUCED METABOLIC CHANGES IN TUMOR HOST INTERACTION

Increased glycolysis in transformed cells coupled with increased membr ane Na+/H+ exchange produces significant environmental fluctuations in and around tumors, including enhanced local glucose consumption and d ecreased extracellular pH. This paper describes a mechanistic, resourc e-based competition model that examines the effects of these environme ntal changes on tumor-host interaction. By generating a critical param eter (J) for each population at the tumor-host interface, the interact ive dynamics can be predicted. Although necessarily limited by simplif ying assumptions, the model demonstrates that the metabolic changes of transformation and their environmental consequences could confer sign ificant advantages on tumor populations by decreasing their J value an d, through the generation of glucose and DH 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 consist ently demonstrated in human tumors in situ, provide a potential mechan ism of tumor invasion that is simple, complete, and sufficiently gener al to apply to many classes of tumors. The model explicitly predicts t hat in situ measurement of tumor glucose utilization and H+ production will determine prognosis. Furthermore, it predicts therapies that chr onically reduce tumor glucose utilization and/or H+ production or incr ease the buffering capacity in normal tissue will be effective in tumo r prevention and tumor treatment.