Modeling bone Metastasis of Cancer in Vitro U...

ABSTRACT

Bone metastasis is a process by which tumor cells leave their site of initiation, invade the surrounding extracellular matrix, travel through the blood circulation, and ultimately metastasize to the bone. While studies have modeled different aspects of this process with respect to physical interactions and signaling between cells, a model system that faithfully mimics the process of bone metastasis in vitro has not been demonstrated. Here, we have modeled bone metastasis in vitroby establishing a triple-coculture system with cell culture inserts. We have incorporated the different constituents involved in the process, including cancer cells, endothelial cells, bone cells, and extracellular matrix proteins, in a single system. Using prostate cancer cells as an example, we have successfully demonstrated transendothelial migration towards the bone cells using this method. This protocol will aid in a better understanding of the complexity of bone metastasis at both the cellular and molecular level.