Detection of Spontaneous Bone Metastases of Solid Human Tumor Xenografts in Mice

The formation of bone metastases from solid primary tumors comprises several processes following each other in a sequential order in terms of the metastatic cascade. The most widely used preclinical models of bone metastasis formation do not reflect this pathophysiological situation as they are based on intracardiac (left ventricle) or intracaudal artery injection of tumor cells. These attempts circumvent all early steps of the metastatic cascade taking place within primary tumors (e.g., epithelial-mesenchymal transition), the passage of circulating tumor cells through upstream organ "filters" like the lung, and the initial establishment of single disseminated tumor cells/cell clusters within the bone marrow. In this chapter, we describe how the entire cascade of bone metastasis formation can be modelled in vivo using bioluminescence techniques. The cascade ranges from the formation of a primary tumor to the outgrowth of single disseminated tumor cells to micro-metastases within the bone marrow. In addition, we describe how the disseminated tumor cells and bone metastases can be visualized by histological and immunohistochemical staining. The described methodology provides the opportunity to investigate the basic mechanisms of spontaneous bone metastasis formation of solid human tumors in partly immunodeficient hosts in vivo.