Cooperation and competition in the dynamics of tissue architecture during homeostasis and tumorigenesis

Abstract

The construction of a network of cell-to-cell contacts makes it possible to characterize the patterns and spatial organization of tissues. Such networks are highly dynamic, depending on the changes of the tissue architecture caused by cell division, death and migration. Local competitive and cooperative cell-to-cell interactions influence the choices cells make. We review the literature on quantitative data of epithelial tissue topology and present a dynamical network model that can be used to explore the evolutionary dynamics of a two dimensional tissue architecture with arbitrary cell-to-cell interactions. In particular, we show that various forms of experimentally observed types of interactions can be modelled using game theory. We discuss a model of cooperative and non-cooperative cell-to-cell communication that can capture the interplay between cellular competition and tissue dynamics. We conclude with an outlook on the possible uses of this approach in modelling tumorigenesis and tissue homeostasis.

Geometrical and topological analysis ofin vivoconfocal microscopy images reveals dynamic maturation of epidermal structures during the first years of life

“…The nearest-neighbors probability distribution qualitatively resembles the organization of cells arising from a cooperators model, with the number of nearest neighbors ranging from three to eight with a maximum at six. 15 This is different from the defector model, typically representing epithelial cancers where the cells tend to adopt a cheating or defective behavior as opposed to cooperation. In a defector model, the cells replicate and differentiate in an uncontrolled way, resulting in a probability distribution more shifted toward higher values, including a small but measurable number of cells having 10 nearest neighbors.…”

“…Such analysis has been successfully used for the segmentation of epithelial cancers from healthy tissue in digitized histological images 14 and epithelial organizations across different species and kingdoms of life. 15 Another useful parameter is the average number of Delauney nearest neighbors. It has been shown that in many complex cellular structures, cells are most likely to have six neighbors, 16,17 while in other organization types, they might have four or even nine (tumors, for instance).…”

Cooperation among cancer cells as public goods games on Voronoi networks

“…While regular lattices neglect the importance of variation in connectivity, scale-free networks are not appropriate if players are distributed on a planar network. The distribution of cells in biological tissues resembles a Voronoi diagram [Lewis 1928, Honda 1978, Gibson & Gibson 2009, Csikász-Nagy et al 2013] rather than a regular lattice or a scale-free network.…”

“…A Voronoi network is defined as a group of such node-joining segments [ Figure 1]. The average connectivity of Voronoi networks is 6, with a unimodal distribution in which fewer than 4 or more than 8 connections are very rare -similar to what is observed in biological samples, both within and among species [Lewis 1928, Gibson & Gibson 2009, Csikász-Nagy et al 2013.…”

“…Voronoi tesselations have been used [Rejniak & Anderson 2011, Csikász-Nagy et al 2013] to simulate the growth of multicellular spheroids [Schaller & Meyer-Hermann 2005, Beyer & MeyerHermann 2009 and the development of colorectal tumors [Meineke et al 2001, Van Leeuwen et al 2009], but not in the study of cooperation between cancer cells, or, more in general, in evolutionary game theory. A preliminary analysis of cooperation on Voronoi networks with a fixed diffusion range has been included in a recent experimental study of IGF-II production in pancreatic cancer [Archetti et al 2015].…”