Assessment of intra-tumor heterogeneity in a two-dimensional vascular tumor growth model

TL;DR

This paper introduces a detailed two-dimensional continuum model of tumor growth that considers multiple tissue phases, including cancer cell maturity and vasculature development, to better understand tumor heterogeneity and growth dynamics.

Contribution

The study develops a novel multi-phase continuum model incorporating cell maturity and vasculature, providing insights into tumor heterogeneity and growth mechanisms.

Findings

Mature cancer cells are spatially separated from young cells, forming a protective shield.

Higher mitosis rates in young cancer cells accelerate tumor growth.

The model predicts distinct spatial distributions of tumor cell sub-phases.

Abstract

We present a two-dimensional continuum model of tumor growth, which treats the tissue as a composition of six distinct fluid phases; their dynamics are governed by the equations of mass and momentum conservation. Our model divides the cancer cells phase into two sub-phases depending on their maturity state. The same approach is also applied for the vasculature phase, which is divided into young sprouts (products of angiogenesis), and fully formed-mature vessels. The remaining two phases correspond to healthy cells and extracellular material (ECM). Furthermore, the model foresees the existence of nutrient chemical species, which are transferred within the tissue through diffusion or supplied by the vasculature (blood vessels). The model is numerically solved with the Finite Elements Method and computations are performed with the commercial software Comsol Multiphysics. The numerical simulations predict that mature cancer cells are well separated from young cancer cells, which form a protective shield for the growing tumor. We study the effect of different mitosis and death rates for mature and young cancer cells on the tumor growth rate, and predict accelerated rates when the mitosis rate of young cancer cells is higher compared to mature cancer cells.