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. We have used a range of transcriptional reporters to evaluate the signalling and differentiation status of invasive and metastatic cells. We observe that numerous changes in cell state occur during metastasis. In a breast cancer model this has shown how transient and localised TGFβ signalling facilitates metastasis. While in melanoma models TGFβ, SRF and Notch signalling are all increased in invasive sub-populations of cells. Further analysis reveals that differentiation hierarchies remain even in aggressive melanoma models.