Highjacked tissue regeneration as a unifying principle of cancer host interaction
Ilaria Malanchi
Francis Crick Institute, London (UK)
Metastatic relapse can occur months to years after the cancer is first diagnosed, and it relies on the reactivation of disseminated tumour cells (DTCs) that have lied dormant in secondary organs. The acquisition and maintenance of a dormancy phenotype are tightly regulated by the interaction of
DTCs with their host tissue microenvironment. In the bone, which is an organ where breast cancer displays long period of latency, several cellular components such as stromal, immune and vascular cells can actively support dormancy, but what trigger DTC reactivation is largely unknown. We here present a strategy to engineer a mouse-to-mouse extramedullary (EM) bone, which faithfully mimics endogenous bone and that can induce the acquisition of a dormancy phenotype in highly metastatic breast cancer cells. We characterised the dormant state of metastatic cells and found that they persist in an equilibrium between two distinct transcriptional states: a more abundant quiescent and less abundant proliferative state. We found that that the dynamics between the two dormant states are determined by environmental factors, and that waves of emergency granulopoiesis caused by inflammatory events such as intestinal colitis, expand the proliferative pool, increasing the chance of metastatic outgrowth.