Macrophage Efferocytosis and Prostate Cancer Bone Metastasis

Despite the advancement of prostate cancer PCa research, little is known about the functional role of tumor-associated macrophages in promoting tumor growth in the bone microenvironment. A subpopulation of alternatively activated macrophages, is associated with supporting tumor growth, but the interaction between macrophages and tumor cells in the context of the bone microenvironment is unexplored. Macrophages play a vital role in maintaining tissue homeostasis, by clearing foreign pathogens and apoptotic tumor cells through phagocytosis. As a result of apoptotic cell phagocytosis a specialized process termed efferocytosis, macrophages release transforming growth factor beta, to prevent a pro-inflammatory response. Interestingly, cancer cells exploit this normal process in order to evade the immune system and substantiate its growth. However, the role of bone resident macrophages osteal macrophages, in supporting tumor growth via efferocytosis has not been explored. Hypothesis The hypothesis of this proposal is that osteal macrophagesmonocytes support prostate cancer bone metastasis through the phagocytosis of apoptotic tumor cells efferocytosis.