RT Journal Article
SR Electronic
T1 Edge effects in game theoretic dynamics of spatially structured tumours
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 014233
DO 10.1101/014233
A1 Artem Kaznatcheev
A1 Jacob G. Scott
A1 David Basanta
YR 2015
UL http://biorxiv.org/content/early/2015/01/23/014233.abstract
AB Background Analysing tumour architecture for metastatic potential usually focuses on phenotypic differences due to cellular morphology or specific genetic mutations, but often ignore the cell’s position within the heterogeneous substructure. Similar disregard for local neighborhood structure is common in mathematical models.Methods We view the dynamics of disease progression as an evolutionary game between cellular phenotypes. A typical assumption in this modeling paradigm is that the probability of a given phenotypic strategy interacting with another depends exclusively on the abundance of those strategies without regard local heterogeneities. We address this limitation by using the Ohtsuki-Nowak transform to introduce spatial structure to the go vs. grow game.Results We show that spatial structure can promote the invasive (go) strategy. By considering the change in neighbourhood size at a static boundary – such as a blood-vessel, organ capsule, or basement membrane – we show an edge effect that allows a tumour without invasive phenotypes in the bulk to have a polyclonal boundary with invasive cells. We present an example of this promotion of invasive (EMT positive) cells in a metastatic colony of prostate adenocarcinoma in bone marrow.Interpretation Pathologic analyses that do not distinguish between cells in the bulk and cells at a static edge of a tumour can underestimate the number of invasive cells. We expect our approach to extend to other evolutionary game models where interaction neighborhoods change at fixed system boundaries.