Necrosis and Apoptosis: Distinct Cell Loss Mechanisms in a Mathematical Model of Avascular Tumour Growth

During the initial avascular phase of solid tumour growth. it is the balance between cell proliferation and cell loss that determines whether the tumour colony expands or regresses. Experimentalists have identified two distinct mechanisms that contribute to cell loss. These are apoptosis and necrosis. Cell loss due to apoptosis may be referred to as programmed-cell-death, occurring. for example, when a cell exceeds its natural lifespan. In contrast, cell loss due to necrosis is induced by changes in the cell's microenvironment. occurring, for example, in nutrient-depleted regions of the tumour. In this paper we present a mathematical model that describes the growth of an avascular tumour which comprises a central core of necrotic cells, surrounded by an outer annulus of proliferating cells. The model distinguishes between apoptosis and necrosis. Using a combination of numerical and analytical techniques we present results which suggest how the relative importance of apoptosis and necrosis changes as the tumour develops. The implications of these results are discussed briefly.