Tumour cells coerce host tissue to cancer spread.

A solid tumour is a complex structure and understanding this complexity is required to study the disease progression. Indeed, 90% of cancer deaths are due to metastatic spreading. Two aspects contribute to tumour complexity. One is the synergistic relationship between tumour cells and their associated host tissue, which persistently characterize tumour growth from the onset to metastasis. Another aspect is the heterogeneity of the cancer cells. It is now clear that within a tumour mass there is a hierarchical organization, stemming from a small amount of cells retaining the highest tumorigenic potential, named cancer stem cells (CSCs). Despite being one of the main studied topics in cancer research, CSC definition is still the subject of debate. Functional testing allows their identification, which is the ability of recapitulating the original tumour structure when transplanted in mice, but occasionally generates conflicting results. This has shaped the hypothesis that their key initiation ability is conditioned by their local microenvironment called niche. The CSC identity appears to be a contextual status where the ability to create a favourable supporting microenvironment may become a key hallmark of their tumour initiation capability. Remarkably, as shown in experimental models, the tumour-initiating potential of CSCs is maintained during metastatic progression, when disseminated cancer cells require the creation of their permissive niche to be able to trigger metastatic growth. This review will discuss the most recent findings on metastatic niche establishment and the cooperation between cancer cells and their newly recruited tumour-associated stroma forming the basis of metastatic development.