How Altered Regulation of the Cytoskeleton Promotes Tumour Invasion and Metastasis

Abstract

The acquisition of invasive behaviour enables the tumour cells to move into either the surrounding tissue or the vasculature and thereby spread to other parts of the body. The focus of our research is investigating why cancer cells become invasive and how they move. To study cell motility in this environment we perform intravital multi-photon confocal imaging of tumours in anaesthetised mice. This enables the heterogeneous behaviour of cancer cells to be studied as they transit between primary and secondary sites. It also allows direct visualisation of the interplay between tumour cells, leukocytes, stromal fibroblasts and endothelial cells. To complement intravital imaging, we have established a range of three-dimensional ‘organotypic’ cultures that allow us to model many aspects of the tumour environment in vitro. By using these systems it has become clear that cancer cells in transit between primary and secondary sites have distinct characteristics. We will discuss the changes in cell signalling and differentiation status that occur in disseminating melanoma cells. In particular, we will propose that aspects of the developmental differentiation hierarchy remain even in aggressive melanoma models.