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Many types of solid tumors metastasize to the bone, where it causes significant morbidity and mortality in patients with advanced disease. Bone metastases are not only incurable but also affect bone health which impairs patients' quality of life. In order to understand the mechanisms and develop effective treatments for bone-metastatic disease, it is first necessary to develop animal models that permit the assessment of tumor growth in the bone and progressive structural changes of the bone simultaneously. Longitudinal analysis of bone tumor progression is generally performed by bioluminescent imaging; however, this method is not able to assess progressive structural changes of the bone. Here, we describe a simple method for assessment of bone lesions using a scoring system that takes into account disease burden and bone destruction using longitudinal radiographs., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)

More than 80% of patients with advanced prostate cancer (PCa) experience bone metastasis, which negatively impacts overall survival and patient quality of life. Various mouse models have been used to study the mechanisms of bone metastasis over the years; however, there is currently no model that fully recapitulates what happens in humans because bone metastasis rarely occurs in spontaneous PCa mouse models. Nevertheless, animal models of bone metastasis using several different tumor inoculation routes have been developed to help study bone metastatic progression, which occurs particularly in late-stage PCa patients. This chapter describes the protocols commonly used to develop models of bone metastatic cancer in mice using different percutaneous injection methods (Intracardiac and Intraosseous). These models are useful for understanding the molecular mechanisms of bone metastatic progression, including tumor tissue tropism and tumor growth within the bone marrow microenvironment. Better understanding of the mechanisms involved in these processes will clearly lead to the development of new therapeutic strategies for PCa patients with bone metastases.

The ability of cancer cells to compete with hematopoietic stem cells (HSCs) to target the bone marrow microenvironment, or the HSC niche, during the dissemination process is critical for the development of bone metastasis. Here, we describe the methods for testing the relative potential of cancer cells to compete with HSCs for occupancy of the HSC niche by measuring the peripheral blood level of engrafted HSCs by flow cytometry in mice after bone marrow transplantation and tandem cancer cell inoculation. This method is useful for determining the molecular mechanisms for the roles of HSCs in the regulation of bone metastases.