Abstract
Macrophages play a vital role in maintaining tissue homeostasis through efferocytosis. However, their functional role and pathophysiological contribution to the bone metastatic microenvironment remains unclear. Therefore, we investigated the efferocytic monocyte/macrophage type and its role in supporting PCa bone metastasis. FACS analysis revealed that M2 bone marrow macrophage polarization resulted in increased efferocytosis and pro‐tumorigenic gene expression. Soluble factors released from macrophage efferocytosis increased the PCa cell growth by 30%. Using tumor mouse models, Trabectedin (a chemotherapeutic drug) treatment diminished M2 like macrophages, resulting in decreased tumor metastasis. Clinically, FACS analysis of circulating monocytes isolated from patients with PCa bone metastasis showed a 20% increase in CD68+/CD14+/CD16+ monocytes. Moreover, these phagocytic monocytes presented a 2.5 fold increase in efferocytosis. Tissue analysis revealed high risk PCa tissue expressed significantly higher levels of CD68, which significantly correlated with a high Gleason score. These findings suggest efferocytic M2 like monocytes and macrophages promote prostate cancer bone metastasis.
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