Implantable pre-metastatic niches for the study of the microenvironmental regulation of disseminated human tumour cells

Abstract

Cancer survivors often carry disseminated tumour cells (DTCs), yet owing to DTC dormancy they do not relapse from treatment. Understanding how the local microenvironment regulates the transition of DTCs from a quiescent state to active proliferation could suggest new therapeutic strategies to prevent or delay the formation of metastases. Here, we show that implantable biomaterial microenvironments incorporating human stromal cells, immune cells and cancer cells can be used to examine the post-dissemination phase of the evolution of the tumour microenvironment. After subdermal implantation in mice, porous hydrogel scaffolds seeded with human bone marrow stromal cells form a vascularized niche and recruit human circulating tumour cells released from an orthotopic prostate tumour xenograft. Systemic injection of human peripheral blood mononuclear cells slowed the evolution of the active metastatic niches but did not change the rate of overt metastases, as the ensuing inflammation promoted the formation of DTC colonies. Implantable pre-metastatic niches might enable the study of DTC colonization and proliferation, and facilitate the development of effective anti-metastatic therapies.