Multiscale Modelling of Adhesion, Tumour Heterogeneity and Immune Response in Breast Cancer Invasion

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Understanding the complex mechanisms of cancer invasion in the human body remains one of thegreatest scientific challenges. At the core of this heterotypic cell process stays the biologically multiscalecharacter of cancer invasion, whose dynamics takes place on several interlinked spatial scales, rangingfrom cell-scale molecular signaling to tissue-scale cell population activity. Moreover, research overthe past decades has shown that the immune response plays an important role within cancer invasion.Naturally induced by the heterotypic character of cancer development, tumour heterogeneity is furtherpotentiated by the interactions with tumour-promoting and tumour-suppressing immune cells withinthe tumour microenvironment. On the other hand, cell adhesion (under the impact of various immunecells) plays a major role in tumour spread.This research aims to provide a deeper understanding of cancer invasion through the development ofnovel multiscale modelling focused on cell-adhesion and tumour heterogeneity under the direct impactof various tumour-infiltrating immune cells. This is an interdisciplinary project led jointly by Dr. Trucuand Dr. Eftimie and carried out in collaboration with clinical experts, Prof. Andrew Evans (NinewellsHospital Dundee) and Prof Alastair Thompson (MD Andreson Cancer Centre, University of Texas, USA).Aims and Objectives:Objective 1: Develop a novel multiscale moving boundary model that accounts for cell-cell adhesion byexploring the correlation between tissue-scale cancer motility and cell-scale interactions of calciumsensing receptors and calcium ions;Objective 2: Investigate tumour heterogeneity, by accounting for the role of tumour-infiltrating immunecells, as well as immuno-inflammatory and cancer-associated fibroblasts.Objective 3: Develop a model calibration procedure with imaging data (provided by Prof. Evans and ProfThompson), aiming this way to capture the true boundaries of breast cancer tumours.Objective 4: Investigate analytically the models developed in Objectives 1 &2 via multiscale analysisconcepts such as three-scale convergence