Landscape of Prostate-Specific Membrane Antigen Heterogeneity in Metastatic Prostate Cancer I. Landscape of Prostate-Specific Membrane Antigen Heterogeneity in Metastatic Prostate Cancer I

Prostate-specific membrane antigen (PSMA) has emerged as an important therapeutic target in metastatic castration-resistant prostate cancer (CRPC). However, not all patients respond to PSMA-targeted therapy, in part due to heterogeneity of tumor expression of the target PSMA. Furthermore, loss of PSMA expression develops in up to 15-20% of patients with CRPC, and the underlying mechanisms remain poorly defined. In this study, we developed an orthotopic xenograft model of CRPC using 22Rv1 cell line, we observed lower PSMA expression in liver lesions versus other sites of metastatic disease, suggesting a potential role of the microenvironment in modulating PSMA expression. To facilitate investigation of PSMA-suppression, we cultured and immortalized a liver metastasis of 22Rv1 metastatic xenograft model in vitro as a new cell line (22Rv1-LMD) which remained AR-positive and PSMA-negative. Overall design: Three orthotopic xenograft model replicates were analyzed metastatic tumors at lymph nodes (n=3) and liver (n=6).