Intrinsic cell factors that influence tumourigenicity in cancer stem cells - towards hallmarks of cancer stem cells

TL;DR

This study develops a hybrid computational model to identify phenotypic traits in cancer stem cells that lead to tumorigenesis, aiming to define universal hallmarks applicable across various cancer types.

Contribution

The paper introduces a generalized hybrid cellular automaton model to explore phenotypic traits driving tumor formation, independent of specific genetic mutations.

Findings

Identified phenotype regions causing tissue overgrowth

Model applicable to multiple tissue types

Suggests targeting phenotypic traits for therapy

Abstract

Since the discovery of a cancer initiating side population in solid tumours, studies focussing on the role of so-called cancer stem cells in cancer initiation and progression have abounded. The biological interrogation of these cells has yielded volumes of information about their behaviour, but there has, as of yet, not been many actionable generalised theoretical conclusions. To address this point, we have created a hybrid, discrete/continuous computational cellular automaton model of a generalised stem-cell driven tissue and explored the phenotypic traits inherent in the inciting cell and the resultant tissue growth. We identify the regions in phenotype parameter space where these initiating cells are able to cause a disruption in homeostasis, leading to tissue overgrowth and tumour formation. As our parameters and model are non-specific, they could apply to any tissue cancer stem-cell and do not assume specific genetic mutations. In this way, our model suggests that targeting these phenotypic traits could represent generalizable strategies across cancer types and represents a first attempt to identify the hallmarks of cancer stem cells.