Radial percolation reveals that Cancer Stem Cells are trapped in the core of tumorspheres

Abstract

Using geometrical arguments it is shown that Cancer Stem Cells (CSC) must be confined inside solid tumors under natural situations. Aided by an agent-based model and percolation theory, the probability for a CSC to be at the border of a colony is estimated. This probability is estimated as a function of the CSCs self-renewal probability $p_s$, i.e. the chance that an CSC become non-differentiate after mitosis. In the most common situations, $p_s$ is small and CSCs are mostly destined to produce differentiated cells at a very low rate. The results presented here show that CSCs form a small core in the center of the cancer cell colony, becoming quiescent due to the lack of space to proliferate, which stabilizes their population size. This result provides a simple explanation for the CSC niche size that dispenses with the need of quorum sensing or other proposed signalling mechanisms. It is also supports the hypothesis that metastases are likely to start at the very beginning of the tumoral development.