Cell size-proliferation relationship in rat glioma cells

The homeostasis of the central nervous system is highly controlled by glial cells and is dramatically altered in the case of glioma. In this respect, the complex connection between cell size and division is of particular importance and needs clarifying. In order to investigate this connection, cell number and volume were measured in C6 rat glioma cells under different experimental conditions, including continuous cell culture, Cl− channel blockade, and anisotonicity, and in the presence of an inhibitory conditioned medium collected from cell cultures or in a medium containing a low level of fetal calf serum. The rate of cell proliferation changed with cell volume in a bell-shaped manner, so that it is optimal within a cell volume window and appears to be controlled by low and high cell size checkpoints. The cell size-proliferation relationship can be defined by Boltzmann-like equations, which may reflect the effects of macromolecular crowding on proteins controlling the cell cycle progression. Altogether, these observations indicate that glioma cell proliferation is controlled predominantly but not exclusively by cell size-dependent mechanisms. © 2003 Wiley-Liss, Inc.