Models of Prostate Cancer Bone Metastasis
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.
Key wordsBone metastasis Bone marrow microenvironment Mouse model Intracardiac injection Intraosseous injection
This work is directly supported by National Cancer Institute (CA163124, Y. Shiozawa), Department of Defense (W81XWH-14-1-0403 and W81XWH-17-1-0541, Y. Shiozawa), the Wake Forest Baptist Comprehensive Cancer Center Internal Pilot Funding (Y. Shiozawa), and the Wake Forest School of Medicine Internal Clinical and Translational Science Institute Pilot Funding (Y. Shiozawa). Y Shiozawa is supported as the Translational Research Academy which is supported by the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, through Grant Award Number UL1TR001420. This work is also supported by the National Cancer Institute’s Cancer Center Support Grant award number P30CA012197 issued to the Wake Forest Baptist Comprehensive Cancer Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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