Investigating cholesterol transfer between macrophages and prostate cancer cells 2736

Abstract Description BACKGROUND Prostate cancer (PC) progression is closely tied to androgen receptor activity. While androgen deprivation therapy (ADT) initially shows efficacy, 20-30% of patients develop resistance within 5 years. Previous studies in mice implicated macrophages in this resistance by transferring cholesterol, a critical molecule for androgen production. This study aims to uncover the mechanism of cholesterol transfer to identify new therapeutic targets to enhance ADT effectiveness. Methods PC cell lines were co-cultured with primary macrophages or RAW264.7 cells labeled with fluorescent cholesterol. The transfer of cholesterol was monitored using flow cytometry and live microscopy. Results Within 24 hours, PC cells acquired cholesterol from macrophages in a contact-dependent manner. This process was independent of macrophage polarization or scavenger receptor SR-B1, which is often upregulated in PC. Live imaging revealed direct transfer of cholesterol-rich plasma membrane from macrophages to PC cells. This was further confirmed by labeling macrophage plasma membranes and tracking the transfer of surface receptors and vital organelles, which increased PC cell proliferation in vitro. Conclusion Macrophages promote androgen production in PC cells by transferring cholesterol-rich plasma membranes via direct contact. Future research will explore the molecular drivers of this process through genomic screens and investigate its role in PC growth and resistance to ADT. Funding Sources Supported by Mike Slive Foundation and Miles for Moffitt. Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)