Efferocytosis and prostate cancer skeletal metastasis: implications for intervention

When tumor cells disseminate to the skeleton, they are bathed in a rich milieu of hematopoietic cells. Bone marrow myeloid cells as resident macrophages appear poised to engulf apoptotic tumor cells in a manner similar to when they engulf normal apoptotic cells during development and homeostasis, a process termed efferocytosis. Intriguingly we identified a different program of events in a macrophage when it engulfs an apoptotic cancer cell versus a non-cancer cell [1]. Upon efferocytosis of an apoptotic cancer cell NF-κB and Stat3 transcriptional machinery was activated and led to pro-inflammatory cytokine production, especially CXCL5, versus the anti-inflammatory cytokines normally attributed to efferocytosis. The resulting pro-inflammatory environment fueled further cancer cell growth hence implicating apoptotic cell clearance via tumor-associated macrophages in supporting tumorigenesis. Such a destructive cascade has previously been hinted at [2] but the entirety of the events and the human data to support it was described for the first time for prostate cancer skeletal metastasis [1]. Importantly, this destructive cascade provides clues for potential therapeutic intervention as suggested in (Figure (Figure11)