Macrophages promotion of anti-androgen resistance and lineage plasticity in prostate cancer

Abstract

One of the biggest challenges in the clinical care of prostate cancer (PCa) is the development of castration-resistant prostate cancer (CRPC). Lineage plasticity has been identified as a crucial mechanism to promote CRPC. Here we identify macrophages secreted factors drives castration-resistance and promotes lineage plasticity. These factors increased the resistance of PC cells towards enzalutamide and promoted the transition of PC cells from luminal state to basal, neuroendocrine, and stem-like state. These provided a new mechanism of tumour microenvironment induced anti-androgen resistance of prostate cancer and promising candidate therapeutic target for CRPC.