An extramedullary bone model to study metastatic dormancy reveals a piecemeal model for metastatic reactivation.

We found that an inflammatory mediator expressed by neutrophils progenitors, HMGB2, can contribute to nudging DTCs into an increased proliferation. Indeed, waves of emergency granulopoiesis expanding the neutrophils pool caused by inflammatory events such as intestinal colitis, expanded the proliferative pool of DTCs without resulting in a direct outgrowth. However, these events, progressively augmented the amount of DTCs in the bone, increasing the chance of overt metastasis.

Therefore, this study proposes a piecemeal model of metastatic reactivation, where subsequent inflammatory events challenging the bone environment progressively increase the likelihood of outgrowth over time as opposed to a sudden switch from dormancy to metastasis.