Bioengineered scaffolds as a tool to decode the complexity of cancer cell interactions in vivo
File(s)
Author(s)
Rizou, Tatiana
Type
Thesis
Abstract
Following primary tumour removal, many cancer types undergo delayed relapse at distant sites, and this represents the leading cause of cancer related death. It is now apparent that cancer cells not only change their local tissue environment, but also the primary tumour can perturb distant tissues creating a more permissive environment for disseminating cancer cells. Towards a deeper understanding of metastatic growth, we set out to create an artificial system that would allow us to manipulate and dissect key aspects of cancer cell interactions in vivo. Here we successfully engineer an implantable biomaterial scaffold, with defined physicochemical properties. This scaffold integrates with the host to create a biocompatible microenvironment in vivo, incorporating stromal cells, endothelial cells, and immune cells, with macrophages as the predominant infiltrating population. In the presence of a primary fat pad tumour, our scaffold achieves to attract and capture spontaneously disseminated tumour cells from the circulation, which subsequently alter the surrounding cellular composition of the scaffold, by increasing the level of non-immune cells. Leveraging the full functionality of the scaffolds, we show that increasing the stiffness of the scaffold or functionalisation of the scaffold with the pro-angiogenic factor VEGF leads to a difference in their cellular infiltrate and subsequent increased cancer cell seeding. Collectively, this tool allows us to modify specific parameters of the disseminating cancer cell niche revealing this way their contribution to different aspects of cancer cell growth.
Version
Open Access
Date Issued
2024-03-25
Date Awarded
2025-01-01
License URL
Advisor
Malanchi, Ilaria
Stevens, Molly Morag
Publisher Department
Bioengineering
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)