Exosome carrying PSGR promotes stemness and epithelial-mesenchymal transition of low aggressive prostate cancer cells

Aim: Prostate-specific G-protein coupled receptor (PSGR) in prostate cancer (Pca) are associated with poor overall survival. However, the effect of exosomal PSGR on PCa metastasis remains unknown. Main methods: The effect of exosome derived from PSGR-overexpressed PC3 cells (PC3 (PSGR+) exosomes) on migration, invasion, epithelial-mesenchymal transition (EMT) and stemness of low invasive cells (LNCaP and RWPE-1) was assessed. Transcriptome sequencing was performed to identify differentially expressed (DE) mRNAs in low invasive cells incubated by PC3 (PSGR+) exosomes or negative control (NC) exosomes. Key findings: The PSGR was stably overexpressed in PC3 cells. The PC3 (PSGR+) exosomes were internalized in LNCaP and RWPE-1 cells, and significantly promoted cells migration and invasion. The expression of E-cadherin was decreased, and Vimentin, Snail, SOX2 and OCT4a was increased in low invasive cells after PC3 (PSGR+) exosome incubation. Additionally, a total of 993 and 1170 DE mRNAs were respectively identified in LNCaP and RWPE-1 cells after PC3 (PSGR+) exosome incubation, and 5 upregulated mRNAs and 11 down regulated mRNAs were shared. The DE mRNAs were predominantly implicated in "activation of Rho GTPase activity" and "response to zinc ion" in LNCaP cells, and "extracellular matrix organization" and "patterning of blood vessels" in RWPE-1 cells. The KEGG analysis showed the DE mRNAs were enriched in pathways associated with EMT such as "Adherens junction", "Cell adhesion molecules (CAMs)" and "Focal adhesion". Significance: Exosomal PSGR promoted migration, invasion, stemness and epithelial-mesenchymal transitions, and reshaped the mRNAs profiling of LNCaP and RWPE-1 cells.