A facile, in vitro 384-well plate system to model disseminated tumor cells in the bone marrow microenvironment

Abstract

Bone marrow disseminated tumor cells (DTCs) are dormant cancer cells that harbor themselves in a bone marrow niche for years after patient remission before potentially returning to a proliferative state, causing recurrent cancer. DTCs reside in bone marrow environments with physiologically important mesenchymal stem cells that are often negatively affected by chemotherapy treatments. Currently, there are very few models of DTCs that recapitulate their dormant phenotype while producing enough samples to accurately quantify cancer and surrounding stromal cell behaviors. We present a three-dimensional spheroid-based model system that uses dual-color bioluminescence imaging to quantify differential cell viability in response to various compounds. We successfully screened for compounds that selectively eliminated cancer cells versus supportive stromal cells and verified results with comparison to efficacy in vivo. The spheroid coculture system successfully modeled key aspects of DTCs in the bone marrow microenvironment, facilitating testing for compounds to selectively eliminate DTCs.