Growth of mammalian multicellular tumor spheroids.

The in vitro growth of small (0.05 to 3 mm diameter) avascular multicellular tumor spheroids from six rodent and two human tumor lines has been analyzed. Surprisingly, the radial increase of multicellular tumor spheroids is linear with time after a brief initial period of geometric growth. These multicellular tumor spheroids are shown to have a constant thickness of proliferative outer crust and of middle nonproliferative but viable mantle. An analytical model for their growth is developed which explains the growth pattern. This constant crust thickness model leads to a progressively diminishing growth fraction as radius increases and should be applicable to such early growth of micrometastases in vivo. The model also provides a procedure for determining cell cycle time.