Reciprocal Interactions between Multiple Myeloma Cells and Osteoprogenitor Cells Affect Bone Formation and Tumor Growth.

摘要

Clonal proliferation of plasma cells within the bone marrow (BM) affects local cells, such as mesenchymal stromal cells (MSCs), leading to osteolysis and fatality in multiple myeloma (MM). Consequently, there is an urgent need to find better mechanisms of inhibiting MM growth and osteolytic lesion development. To meet this need and accelerate clinical translation, better models of MM within the BM are required. We developed a clinically-relevant, 3D myeloma BM co-culture model that mimics bone cell-cancer cell interactions within the bone microenvironment. The co-culture model and clinical samples were utilized to investigate myeloma growth, osteogenesis inhibition, and myelomainduced abnormalities in MM-MSCs. This platform demonstrated myeloma support of capillary-like assembly of endothelial cells and cell adhesion mediated-drug resistance (CAM-DR). Also, distinct normal donor (ND)- and MM-MSC miRNA signatures were identified and used to uncover osteogenic miRs of interest for osteoblast differentiation. More broadly, our 3D platform provides a simple, clinically-relevant tool to model cancer growth within the bone, useful for investigating skeletal cancer biology, screening compounds, and exploring osteogenesis. Our identification and efficacy validation of novel, bone anabolic miRs in MM opens the floodgate for novel approaches to cancer.