Cell migration is essential for sustained growth of keratinocyte colonies: the roles of transforming growth factor-alpha and epidermal growth factor

Abstract

In common methods of cell cultivation, multiplication takes place in cells distributed uniformly or in small colonies and the number of cells increases exponentially. In contrast, an isolated colony of coherent epidermal keratinocytes, as it grows larger, departs drastically from exponential growth, and instead increases its radius at a constant rate over time. The rate of increase of colony radius is 8-fold greater in the presence of epidermal growth factor (EGF) and 10-fold greater in the presence of transforming growth factor-alpha (TGF-alpha): the resulting megacolonies may become 30-50 times greater in area and cell number than colonies grown in the absence of the growth factors. Growth of a colony depends on outward migration of the rapidly proliferating cells located in a thin rim close to the colony perimeter. The effect of EGF and TGF-alpha in promoting multiplication must depend on their ability to increase the rate of this cell migration.