Figure 3

The flowchart of control in the multiscale model of CSC-initiated tumor development. (A) Each cell evolves according to their life cycle under the conditions confined by the PDE system. Necrosis occurs when cell death is induced by hypoxia. (B) Hierarchical organization of different cell subtypes and their proliferative kinetics. Cancer stem cells (CSC) expand their own population by symmetric proliferation to two identical daughter cells still with CSC-like traits and expand the whole tumor through asymmetric differentiation to progenitor cells (PC) and terminally differentiated cells (TC) in this model. Similarly, PCs contribute to the constitution of the tumor in a similar way, but do not reversibly produce CSCs according to the hierarchical organization hypothesis. The TCs are assumed to either proliferate or be apoptotic at each time point without ability to divide into any other subtypes. The parameters above the arrows indicate the occurrence probability of the referred event at each time point.