A mathematical model describing consequences of abnormally high levels of epidermal growth factor receptor on the proliferation of neoplastic cells.

ABSTRACT

Recent laboratory and clinical data suggest that some human neoplasms exhibit unusually high levels of cell-surface receptors for epidermal growth factor, and that this abnormality is associated with rapid cellular proliferation and poor prognosis. We propose that the existence of an abnormally high number of mitogen receptors is not merely correlated with rapid proliferation but is pathophysiologically responsible for such behavior. Cells with high levels of mitogen receptors may be rendered 'hypersensitive' to mitogenic stimuli, and hence may be stimulated to divide even when ambient mitogen concentrations are at a low 'background' level, insufficient to prompt the division of cells with a normal number of receptors. To investigate this hypothesis further, we have developed a mathematical model that describes proliferative behavior of cells as a function of mitogen concentration and receptor number. The model enables us to simulate the proliferative behavior of cells with various receptor levels at various mitogen concentrations and predicts a growth advantage associated with excess mitogen receptors. Computer simulations based on the model are consistent with previously published experimental data. This work provides support for the view that overexpression of genes encoding normal growth factor receptors can contribute to the inappropriate proliferation of neoplastic cells.