Cancer tissue is known to be composed of heterogeneous cancer cells and various stromal cells, and these cells are dynamically interacting each other. Although interaction between cancer cells and associated stromal cells in terms of tumour growth and resistance to anticancer drugs had been well studied, our understanding of association between heterogeneous cells in the context of invasion was very limited.
Invasion of cancer cells into neighbouring tissue is a critical first step of metastasis, which is the leading cause of mortality among cancer patients. In the past decade, advanced imaging studies of both cultured cells and cells in living animals had revealed that cancer cells invade either as individually single cell or as well-organised adherent collectives. Extensive studies had provided substantial amount of insight into the molecular mechanism of how single cell moves; how to change their shape, activate the signalling pathway inside of the cells, and regulate cytoskeletal dynamics during migration/invasion. However, our understanding of collective invasion was less advanced. This partly reflected the likelihood that it is not a single invasive behaviour, but a combination of different behaviours. An additional complication was the well-documented heterogeneity of cancer cells even within a single tumour. This diversity may be genetic, epigenetic, related to ‘cancer stem cell’ hierarchies, or caused variation in local environmental cues. Therefore, to understand the process of collective cancer invasion one must consider possible heterogeneity between cancer cells in the cluster. This requires considering concepts such as relative migratory fitness, cell sorting, and cell competition. The objective of this project was to study collective cell migration involving heterogeneous populations of cells by using complementary experimental and computational models of collective cancer cell invasion.
