An integrated approach to modelling cancer metastasis

The spread of cancer to distant sites, metastasis, is responsible for the majority of cancer related deaths. Metastasis is a complex process comprising a number of steps and mechanisms which take place over time. Due to the temporal and extemperaneous nature of metastasis it has proved difficult to study. Current models are limited in their application and there is a need to develop new models which provide a better and more meaningful biological context for the study of metastasis. Taking a tissue engineering approach, this project has sought to develop a set of in vitro models for the exploration of cancer metastasis in three dimensions. Two collagen based assays were developed to allow the exploration of metastasis in a three dimensional (3D) environment. A simple collagen based assay was developed to create multiple regions of interest, allowing the study of cell migration, invasion and colonization in two dimensions, three dimensions and at border zones. Compression of collagen was used to construct a stiffer more elastic 3D in vitro context and this assay was developed to provide multiple regions of interest for the study of metastasis in a more structured and biologically relevant environment. The chick chorioallantoic membrane (CAM) assay was explored as an in vivo model for the study of metastasis however this allowed only a short time period for study. However, the decellularization of CAM tissue provided a novel and useful 3D context which could be used for the study of metastatic mechanisms in direct comparison to the in vivo model but over longer time periods