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

乳腺癌侵袭中粘附、肿瘤异质性和免疫反应的多尺度建模

基本信息

批准号：
2122945
负责人：
金额：
--
依托单位：
University of Dundee
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2018
资助国家：
英国
起止时间：
2018 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=studentship-2122945
关键词：
Multiscale Modelling Adhesion Tumour Heterogeneity

项目摘要

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

了解癌症侵入人体的复杂机制仍然是最大的科学挑战之一。这种异型细胞过程的核心是癌症侵袭的生物学多尺度特征，其动力学发生在几个相互关联的空间尺度上，从细胞尺度的分子信号传导到组织尺度的细胞群体活动。此外，过去几十年的研究表明，免疫反应在癌症侵袭中起着重要作用。肿瘤异质性是由癌症发展的异型特征自然诱导的，肿瘤微环境中促肿瘤和抑肿瘤免疫细胞的相互作用进一步增强了肿瘤异质性。另一方面，细胞粘附（在各种免疫细胞的影响下）在肿瘤扩散中起着重要作用。本研究旨在通过开发新的多尺度模型来更深入地了解癌症侵袭，该模型专注于各种肿瘤浸润免疫细胞直接影响下的细胞粘附和肿瘤异质性。这是一个跨学科的项目，由Trucu博士和Eftimie博士共同领导，并与临床专家Andrew Evans教授合作开展。（NinewellsHospital邓迪）和阿拉斯泰尔·汤普森教授（MD Andreson Cancer Centre，University of Texas，USA）。开发一种新的多尺度移动边界模型，通过探索组织尺度癌症运动与细胞粘附之间的相关性，目的2：通过解释肿瘤浸润免疫细胞以及免疫炎症和癌症相关成纤维细胞的作用，研究肿瘤异质性。目的3：利用成像数据开发模型校准程序（由Evans教授和Thompson教授提供），旨在通过这种方式捕捉乳腺癌肿瘤的真实边界。通过多尺度分析概念（如三尺度收敛）分析研究目标1和目标2中开发的模型