Malignancy through cooperation: an evolutionary game theory approach

Abstract

Traditional cancer initiation theory propounds evolution of a monoclonal population of fully transformed tumour cells to form a malignant tumour. Cooperation between surrounding stroma and the tumour also often leads to malignancy. This cooperation may exist as a result of sharing of growth signals or growth factors secreted by stromal cells, which can cause those with proliferative phenotypes to switch to motile phenotypes. Mathematical models of sharing of growth factors between cancer stem cells and stromal cells can allow for deeper understanding of tumourigenesis through cooperation. The study presented here describes a novel evolutionary game theoretical approach to investigate emergence of malignancy through interactions among cells of three different phenotypes, one of which produces growth factors. Three different scenarios have been considered, and types of behaviour of the three phenotypes during interactions, have been modelled in terms of cost and benefit variables. Phenotypic compositions of such a tumour at equilibrium have been analysed, and evolution of the population, with respect to time, has been investigated. Results suggest the role of cooperation in forming a malignant tumour and show, in all three cases, that emergence of triple polymorphism, two-strategy polymorphism, and fixation of one phenotype, were possible at equilibrium. The models also suggest that under certain conditions, one phenotype may be completely eliminated from the population, thus leading to new possibilities for potential treatments. This study explains some current experimental findings from a theoretical viewpoint, and may provide new approaches for future research in oncology.