Phenotype divergence and cooperation in isogenic multicellularity and in cancer

TL;DR

This paper explores how mechanisms of phenotype divergence and cooperation in multicellularity are altered in cancer, using mathematical models to compare evolutionary emergence and tumor development.

Contribution

It introduces mathematical models analyzing the reversal and hijacking of multicellularity mechanisms in cancer, linking biological, mathematical, and philosophical perspectives.

Findings

Cancer hijacks multicellularity mechanisms

Models show partial reversal of differentiation and cooperation in tumors

Evolutionary and developmental contexts are contrasted

Abstract

We discuss the mathematical modelling of two of the main mechanisms which pushed forward the emergence of multicellularity: phenotype divergence in cell differentiation, and between-cell cooperation. In line with the atavistic theory of cancer, this disease being specific of multicellular animals, we set special emphasis on how both mechanisms appear to be reversed, however not totally impaired, rather hijacked, in tumour cell populations. Two settings are considered: the completely innovating, tinkering, situation of the emergence of multicellularity in the evolution of species, which we assume to be constrained by external pressure on the cell populations, and the completely planned-in the body plan-situation of the physiological construction of a developing multicellular animal from the zygote, or of bet hedging in tumours, assumed to be of clonal formation, although the body plan is largely-but not completely-lost in its constituting cells. We show how cancer impacts these two settings and we sketch mathematical models for them. We present here our contribution to the question at stake with a background from biology, from mathematics, and from philosophy of science.