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

TL;DR

This study uses geometrical, agent-based, and percolation theory models to demonstrate that Cancer Stem Cells are confined to the tumor core, explaining their quiescence and the initial development of metastases.

Contribution

It introduces a geometrical and percolation-based framework to explain CSC confinement and niche size without relying on signaling mechanisms.

Findings

CSC form a small, quiescent core in tumor centers

CSC probability at the border is low when self-renewal probability is small

Metastases likely originate early in tumor development

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.