Modeling the emergence of phenotypic heterogeneity in vascularized tumors

Abstract

We present a mathematical study of the emergence of phenotypic heterogeneity in vascularized tumors. Our study is based on formal asymptotic analysis and numerical simulations of a system of nonlocal parabolic equations that describes the phenotypic evolution of tumor cells and their nonlinear dynamic interactions with the oxygen, which is released from the intratumoral vascular network. Numerical simulations are carried out both in the case of arbitrary distributions of intratumor blood vessels and in the case where the intratumoral vascular network is reconstructed from clinical images obtained using dynamic optical coherence tomography. The results obtained support a more in-depth theoretical understanding of the eco-evolutionary process which underpins the emergence of phenotypic heterogeneity in vascularized tumors. In particular, our results offer a theoretical basis for empirical evidence indicating that the phenotypic properties of cancer cells in vascularized tumors vary with the distance from the blood vessels, and establish a relation between the degree of tumor tissue vascularization and the level of intratumor phenotypic heterogeneity.