Multiscale Modelling of Adhesion, Tumour Heterogeneity and Immune Response in Breast Cancer Invasion
Lead Research Organisation:
University of Dundee
Department Name: Mathematics
Abstract
Understanding the complex mechanisms of cancer invasion in the human body remains one of the
greatest scientific challenges. At the core of this heterotypic cell process stays the biologically multiscale
character of cancer invasion, whose dynamics takes place on several interlinked spatial scales, ranging
from cell-scale molecular signaling to tissue-scale cell population activity. Moreover, research over
the 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 further
potentiated by the interactions with tumour-promoting and tumour-suppressing immune cells within
the tumour microenvironment. On the other hand, cell adhesion (under the impact of various immune
cells) plays a major role in tumour spread.
This research aims to provide a deeper understanding of cancer invasion through the development of
novel multiscale modelling focused on cell-adhesion and tumour heterogeneity under the direct impact
of various tumour-infiltrating immune cells. This is an interdisciplinary project led jointly by Dr. Trucu
and Dr. Eftimie and carried out in collaboration with clinical experts, Prof. Andrew Evans (Ninewells
Hospital 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 by
exploring the correlation between tissue-scale cancer motility and cell-scale interactions of calcium
sensing receptors and calcium ions;
Objective 2: Investigate tumour heterogeneity, by accounting for the role of tumour-infiltrating immune
cells, as well as immuno-inflammatory and cancer-associated fibroblasts.
Objective 3: Develop a model calibration procedure with imaging data (provided by Prof. Evans and Prof
Thompson), 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 analysis
concepts such as three-scale convergence
greatest scientific challenges. At the core of this heterotypic cell process stays the biologically multiscale
character of cancer invasion, whose dynamics takes place on several interlinked spatial scales, ranging
from cell-scale molecular signaling to tissue-scale cell population activity. Moreover, research over
the 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 further
potentiated by the interactions with tumour-promoting and tumour-suppressing immune cells within
the tumour microenvironment. On the other hand, cell adhesion (under the impact of various immune
cells) plays a major role in tumour spread.
This research aims to provide a deeper understanding of cancer invasion through the development of
novel multiscale modelling focused on cell-adhesion and tumour heterogeneity under the direct impact
of various tumour-infiltrating immune cells. This is an interdisciplinary project led jointly by Dr. Trucu
and Dr. Eftimie and carried out in collaboration with clinical experts, Prof. Andrew Evans (Ninewells
Hospital 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 by
exploring the correlation between tissue-scale cancer motility and cell-scale interactions of calcium
sensing receptors and calcium ions;
Objective 2: Investigate tumour heterogeneity, by accounting for the role of tumour-infiltrating immune
cells, as well as immuno-inflammatory and cancer-associated fibroblasts.
Objective 3: Develop a model calibration procedure with imaging data (provided by Prof. Evans and Prof
Thompson), 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 analysis
concepts such as three-scale convergence
Organisations
People |
ORCID iD |
| Dumitru Trucu (Primary Supervisor) | |
| Szabolcs Suveges (Student) |
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| EP/N509632/1 | 01/10/2016 | 30/09/2021 | |||
| 2122945 | Studentship | EP/N509632/1 | 01/10/2018 | 31/03/2022 | Szabolcs Suveges |
| EP/R513192/1 | 01/10/2018 | 31/03/2024 | |||
| 2122945 | Studentship | EP/R513192/1 | 01/10/2018 | 31/03/2022 | Szabolcs Suveges |
| Description | We addressed the directionality of the macrophages within an invading tumour in a fibrous environment. |
| Exploitation Route | There are several research avenues that we are currently investigating both for a general tumour and for glioblastoma invasion, this being the topic of three other manuscripts that are currently under review. This will bring light to both general and specific questions that researchers in the area will utilize as a platform for further studies. |
| Sectors | Education,Healthcare,Other |