Mathematical Modelling of a Brain Tumour Initiation and Early Development: A Coupled Model of Glioblastoma Growth, Pre-Existing Vessel Co-Option, Angiogenesis and Blood Perfusion

PLoS One. 2016 Mar 2;11(3):e0150296. doi: 10.1371/journal.pone.0150296. eCollection 2016.

Abstract

We propose a coupled mathematical modelling system to investigate glioblastoma growth in response to dynamic changes in chemical and haemodynamic microenvironments caused by pre-existing vessel co-option, remodelling, collapse and angiogenesis. A typical tree-like architecture network with different orders for vessel diameter is designed to model pre-existing vasculature in host tissue. The chemical substances including oxygen, vascular endothelial growth factor, extra-cellular matrix and matrix degradation enzymes are calculated based on the haemodynamic environment which is obtained by coupled modelling of intravascular blood flow with interstitial fluid flow. The haemodynamic changes, including vessel diameter and permeability, are introduced to reflect a series of pathological characteristics of abnormal tumour vessels including vessel dilation, leakage, angiogenesis, regression and collapse. Migrating cells are included as a new phenotype to describe the migration behaviour of malignant tumour cells. The simulation focuses on the avascular phase of tumour development and stops at an early phase of angiogenesis. The model is able to demonstrate the main features of glioblastoma growth in this phase such as the formation of pseudopalisades, cell migration along the host vessels, the pre-existing vasculature co-option, angiogenesis and remodelling. The model also enables us to examine the influence of initial conditions and local environment on the early phase of glioblastoma growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Brain / blood supply*
  • Brain / pathology*
  • Brain / physiopathology
  • Brain Neoplasms / blood supply*
  • Brain Neoplasms / pathology*
  • Brain Neoplasms / physiopathology
  • Computer Simulation
  • Glioblastoma / blood supply*
  • Glioblastoma / pathology*
  • Glioblastoma / physiopathology
  • Hemodynamics
  • Humans
  • Models, Biological
  • Neovascularization, Pathologic / pathology*
  • Neovascularization, Pathologic / physiopathology

Grants and funding

This research is supported by the National Basic Research Program of China (973 Program) (No. 2013CB733800), the National Nature Science Foundation of China (No. 11302050, No. 11272091), and the Nature Science Foundation of Jiangsu Province (No. BK20130593). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.