Tumor growth and progression is a complex phenomenon dependent on the
interaction of multiple intrinsic and extrinsic factors. Necessary for tumor
development is a small subpopulation of potent cells, so-called cancer stem
cells, that can undergo an unlimited number of cell divisions and which are
proposed to divide symmetrically with a small probability to produce more cancer
stem cells. We show that the majority of cells in a tumor must indeed be
non-stem cancer cells with limited life span and limited replicative potential.
Tumor development is dependent as well on the proliferative potential and death
of these cells, and on the migratory ability of all cancer cells. With
increasing number of cells in the tumor, competition for space limits tumor
progression, and in agreement with in vitro observation, the majority of cancer
cells become quiescent, with proliferation primarily occurring on the outer rim
where space is available. We present an agent-based model of early tumor
development that captures the spatial heterogeneity of stemness and
proliferation status. We apply the model to simulations of radiotherapy to
predict treatment outcomes for tumors with different stem cell pool sizes and
different quiescence radiosensitivities. We show by first presuming homogeneous
radiosensitivity throughout the tumor, and then considering the greater
resistance of quiescent cells, that stem cell pool size and stem cell
repopulation during treatment determine treatment success. The results for
tumor cure probabilities comprise upper bounds, as there is evidence that cancer
stem cells are also more radioresistant than other tumor cells. Beyond just
demonstrating the influence of mass effects of stem to non-stem cell ratios and
proliferating to quiescent cell ratios, we show that the spatiotemporal
evolution of the developing heterogeneous population plays a pivotal role in
determining radioresponse and treatment optimization.