Lactate-induced inhibition of tumor cell proliferation.

Culture medium that was recovered from tumor cell or fibroblast cultures during the plateau phase, and that was replenished by addition of glucose, glutamine, and serum and readjustment of pH had a distinct growth-inhibiting effect on monolayer cell cultures. The effect, which was not specific for a given cell strain, may be partially responsible for the "density inhibition" commonly observed in malignant cells grown in monolayer cultures. By modifying fresh growth media, it was shown that the growth inhibition observed can be partly attributed to the accumulation of lactate in the culture medium of plateau phase cells. This substance reduced the plating efficiency and the number of cells per petri dish in the plateau phase. It is concluded that this effect may be used for inducing growth inhibition in tumors in vivo by manipulating the cellular production of lactate and/or by impeding its removal from the cellular microenvironment.