AbstractThe ability to invade its surrounding tissue is one of the acknowledged hallmarks of cancer. This complex multi-scale process is affected by many players of the tumour microenvironment (TME), including the extracellular matrix (ECM) and various stromal cells such as macrophages. One of these key processes is the secretion of matrix degrading enzymes that enables the degradation of the neighbouring ECM and cell-matrix adhesion. By varying the strength of cell-matrix and multiple cell-cell adhesions, cancer cells can spread into the surrounding tissues which combined with an unregulated proliferation results in an uncontrollable, indefinite growth.
This thesis considers a continuous multi-scale moving boundary model for general solid tumours that takes into account the multi-scale interactions between the different cell populations and a two-phase ECM as well as the proteolytic molecular processes taking place along the leading edge of a growing solid tumour. To that end, we investigate how one of the most abundant immune cells in the TME, the macrophages, and their phenotype influence the overall tumour progression, by exploring their multi-scale effects. Moreover, we extend our approach and consider a discrete cell population consisting of individual cancer cells that allows us to further study the complex interaction between the cancer cells and a two-phase ECM as well as the overall shape and migration type of a tumour aggregation. Finally, we apply our general continuous model to a specific type of brain tumour, glioblastomas, using patient-specific brain scans that allows us to investigate the role of brain micro-fibres in a 3-dimensional invading tumour.
|Date of Award
|Engineering and Physical Sciences Research Council
|Dumitru Trucu (Supervisor) & Raluca Eftimie (Supervisor)