Multiscale modeling of glioma pseudopalisades: contributions from the tumor microenvironment

TL;DR

This paper develops a multiscale reaction-diffusion model for glioma pseudopalisades, demonstrating pattern formation under certain conditions and suggesting brain tissue may be undirected for glioma migration.

Contribution

It introduces a novel multiscale modeling framework for glioma pseudopalisades, linking cell-level responses to tissue-scale patterns and comparing different tissue anisotropy effects.

Findings

Patterns form in the PDE model under certain parameters.

Pattern formation depends on tissue anisotropy, with undirected tissue supporting pseudopalisades.

The model provides insights into tumor microenvironment influence on glioma invasion.

Abstract

Gliomas are primary brain tumors with a high invasive potential and infiltrative spread. Among them, glioblastoma multiforme (GBM) exhibits microvascular hyperplasia and pronounced necrosis triggered by hypoxia. Histological samples showing garland-like hypercellular structures (so-called pseudopalisades) centered around the occlusion site of a capillary are typical for GBM and hint on poor prognosis of patient survival. We propose a multiscale modeling approach in the kinetic theory of active particles framework and deduce by an upscaling process a reaction-diffusion model with repellent pH-taxis. We prove existence of a unique global bounded classical solution for a version of the obtained macroscopic system and investigate the asymptotic behavior of the solution. Moreover, we study two different types of scaling and compare the behavior of the obtained macroscopic PDEs by way of simulations. These show that patterns1 (including pseudopalisades) can be formed for some parameter ranges, in accordance with the tumor grade. This is true when the PDEs are obtained via parabolic scaling (undirected tissue), while no such patterns are observed for the PDEs arising by a hyperbolic limit (directed tissue). This suggests that brain tissue might be undirected - at least as far as glioma migration is concerned. We also investigate two different ways of including cell level descriptions of response to hypoxia and the way they are related.