Alternatively activated monocytes/macropahges support prostate cancer skeletal metastasis (397.6)

Abstract

Macrophages play a vital role in maintaining tissue homeostasis, by clearing foreign pathogens and apoptotic tumor cells through phagocytosis (termed eferrcoytosis). The purpose of this study was to determine the bone resident phagocytic macrophage/monocyte(s) that support prostate cancer (PCa) bone metastasis through efferocytosis and TGFβ. Bone marrow macrophages co‐incubated with either apoptotic mimicry beads or apoptotic PCa tumor cells exhibited efferocytosis and displayed a shift to a M2 phenotype. Furthermore, co‐incubation with apoptotic tumor cells resulted in an increase in gene expression of efferocytic markers TGFβ, MERTK and MFG‐E8. From a clinical perspective, patients with malignant PCa expressed higher levels of MFG‐E8, a known efferocytosis facilitator, while co‐localization of CD68+ cells and MFG‐E8 was significantly increased in malignant PCa tissue. Moreover, peripheral blood from patients with PCa bone metastasis showed significantly higher numbers of efferocytic CD68+ and CD14+16‐ monocytes, which significantly correlated with their PSA levels. Together, these results demonstrate that efferocytosis by bone‐derived macrophages elicits a pro‐tumorigenic response that is sufficient to support tumor growth. Moreover, PCa bone metastasis patients exhibit a high alternatively activated efferocytic monocyte population.Grant Funding Source: Supported by PO1CA093900‐10