A multiscale mathematical model of tumour invasive growth

TL;DR

This paper introduces a novel multiscale mathematical model combining tissue-level tumor dynamics with molecular-level enzyme activity to better understand invasive cancer growth patterns.

Contribution

It presents a new two-scale moving boundary model that links tumor morphology changes with cell-scale enzyme dynamics, advancing multiscale cancer invasion modeling.

Findings

Simulates heterogeneous invasion patterns similar to clinical observations

Demonstrates the impact of uPA enzyme dynamics on tumor morphology

Provides a framework for studying multiscale tumor invasion processes

Abstract

Known as one of the hallmarks of cancer [30], cancer cell invasion of human body tissue is a complicated spatio-temporal multiscale process which enables a localised solid tumour to transform into a systemic, metastatic and fatal disease. This process explores and takes advantage of the reciprocal relation that solid tumours establish with the extracellular matrix (ECM) components and other multiple distinct cell types from the surrounding microenvironment. Through the secretion of various proteolytic enzymes such as matrix metalloproteinases (MMP) or the urokinase plasminogen activator (uPA), the cancer cell population alters the configuration of the surrounding ECM composition and overcomes the physical barriers to ultimately achieve local cancer spread into the surrounding tissue. The active interplay between the tissue-scale tumour dynamics and the molecular mechanics of the involved proteolytic enzymes at the cell-scale underlines the biologically multiscale character of invasion, and raises the challenge of modelling this process with an appropriate multiscale approach. In this paper, we present a new two-scale moving boundary model of cancer invasion that explores the tissue scale tumour dynamics in conjunction with the molecular dynamics of the urokinase plasminogen activation system. Building on the multiscale moving boundary method proposed in [58], the modelling that we propose here allows us to study the changes in tissue scale tumour morphology caused by the cell-scale uPA micro-dynamics occurring along the invasive edge of the tumour. Our computational simulation results demonstrate a range of heterogeneous dynamics which are qualitatively similar to the invasive growth patterns observed in a number of different types of cancer, such as the tumour infiltrative growth patterns discussed in [33].