On the Significance of Glucolysis for Cancer Growth, With Special Reference to Morris Rat Hepatomas2

Abstract

Anaerobic fermentation (glycolysis of glucose) was measured in a progressive growth spectrum of normal and host rat livers (zero net growth) through very slowly growing, slowly growing, intermediately growing, and rapidly growing lines of Morris rat hepatomas, maintained as slices in Krebs-Ringer bicarbonate-glucose-pyruvate medium at 37 C with 5% CO₂ in N₂ as gas phase. All hepatoma lines, including even the most slowly growing, showed glucose fermentation values in excess of those of normal or host rat livers. A continuous, positive correlation was observed between in vivo growth rate and in vitro anaerobic glucolytic potential; also, of equal importance, K_m-glucose (concentration of glucose required for half-maximum rate of fermentation) and degree of inhibition by the anti-insulin stilbestrol decreased with increasing growth rate. Recent data of Gullino are cited which provide overwhelming evidence as to the actuality of in vivo fermentation of glucose to lactate by slow-growing hepatomas of the Morris series, compared to in vivo consumption of lactate normally observed with livers. The results reported make clear that a dominant biochemical difference between a normal metabolism and one characteristic of even the lowest degree of malignancy studied involves a critical, however small, increase in glucolytic capacity over that in the normal tissue of origin, in this instance, liver. Progression in malignant growth capacity is associated with increasing fermentation capacity. These results and conclusions confirm and extend the well-known findings of Otto Warburg over the past 40 years and our similar findings made with mouse melanoma spectra and Sanford-Earle tissue culture spectra, and, as reported here, also in the Hilf rat mammary tumor spectrum. Implications of these findings for chemotherapy and hyperthermy therapy of cancers are briefly indicated.