During metastasis, tumour cells exit blood circulation (extravasation) at a site distant to the initial primary tumour site to form a secondary tumour. Recently, Ke Cheng and colleagues described a process that involves remodelling of the vascular wall so that the tumour cell is actively expulsed to exit the lumen, which they called angiopellosis. However, it remained unclear whether tumour cells use angiopellosis-driven extravasation as a group of cells or if cells first dissociate from each other. In their Research Article, these authors now (Allen et al., 2019) employ live imaging in zebrafish and mouse models to address this question and find that both individual tumour cells as well as cell clusters are able to exit blood vessels through angiopellosis. The authors further show that cells from extravasated clusters have a greater ability to proliferate than their individual cell counterparts. In addition, tumour cells that have undergone extravasation as clusters show an increased capacity to form secondary tumours and a unique gene expression profile – in particular for cell adhesion-related genes – which suggests that these clustered cells have unique cellular characteristics. This work challenges the idea that circulating tumour cells can only undergo extravasation as clusters and proposes that the ability of circulating tumour cells to extravasate as a cluster increases their probability to form secondary tumours at distant sites.
