Figure 1.

Mechanobiological design considerations for metastasis-on-a-chip systems mimicking breast cancer metastasis to bone. Breast cancer cells (BCCs) invade the extracellular matrix (ECM), intravasate into blood vessels where they circulate in the vascular system before extravasating into a secondary site, in this case bone, where they grow into secondary tumors in vivo. A breast cancer-mimicking compartment should be made up of appropriate breast cancer cells and a surrounding ECM that will generate physiologically relevant matrix stiffness. A bone-mimicking compartment will consist of bone-residing cells, including mesenchymal stromal cells, osteoblasts, and osteoclasts, as well as key bone ECM components, such as hydroxyapatite. The ECM components included will define the elasticity, topography and chemistry of the matrix. Interconnected, physiologically relevant fluid flow between compartments will allow cancer cell migration to the secondary site and the formation of suitable cytokine/growth factor gradients. Portions of the schematic were produced using Servier Medical Art (smart.servier.com).