Interrelationship among morphology, metabolism, and proliferation of tumor cells in monolayer and spheroid culture.

The proliferative activity of tumor cells is positively correlated with the cellular respiration rate. Thus, a decrease in the proliferative fraction during monolayer growth of EMT6 cells is associated with a decrease in the oxygen consumption rate both per cell and per cellular volume. These changes are paralleled by variations in the morphology of the tumor cells. The cellular volume, the cytoplasmic volume, the number and volume of mitochondria is decreased, whereas the volume of the nucleus remains relatively constant during the transition of cells from the exponential to the plateau growth phase. Similar observations have been made in outer, highly proliferative and inner non-proliferating cells in EMT6 spheroids. However, the local oxygen consumption in this three dimensional, tissue-like assemblage of cells is obviously modified by the cellular packing density leading to a rather uniform oxygen uptake in the proliferating and non-proliferating cell areas.