Influence of geometry on control of cell growth.

The assembled evidence suggests that geometry plays an important role in regulation of cell growth, at least at two levels: (1) For non-transformed individual cells in culture, there may be a continuous range of shapes, from spherical all the way to extremely flat or extended, which correlates with increasing proliferative capacity or increasing ability to respond to serum growth factors. In other words, sensitivity to a variety of mitotic stimulators and growth factors may be modulated by cell conformation. Fully transformed cells appear to lose the modulating effect of shape, and thus are able to proliferate even when spherical. (2) For transformed cells which can grow in three-dimensional populations, the shape of the population itself eventually limits growth. The most likely mechanism is based upon the limiting effects of diffusion gradients of nutrients, oxygen and catabolites which build up across the surface of a three-dimensional population of cells. Tumor cells which are able to make tumour angiogenesis factor (TAF), induce new capillary blood vessels from the host. These vessels penetrate the tumor and permit further rapid growth. In this sense, tumor angiogenesis is a mechanism by which "successful" tumors escape the growth restriction imposed upon three-dimensional cell population by geometry [49].