EGFL7 Inhibits the Immune Response in Metastatic Castration-Resistant Prostate Cancer by Deactivating Endothelial Intercellular Adhesion Molecule-1.

Purpose: Epidermal growth factor-like 7 (EGFL7) has been implicated in various cancers, but its role in different stages of prostate cancer (PCa), particularly metastatic castration-resistant prostate cancer (mCRPC), remains unclear. This study aimed to investigate the biological function of EGFL7 and its association with immune regulation in PCa.

Materials and methods: We quantified EGFL7 and intercellular adhesion molecule-1 (ICAM-1) levels in serum and prostate tissue specimens from patients with benign prostatic hyperplasia (BPH), localized PCa, and mCRPC. To explore its functional role, EGFL7 expression was either silenced or overexpressed in DU145 and PC3 cells using siRNA or pCMV-GFP, respectively. Xenograft experiments were conducted in nude mice using transfected DU145/PC3 cells, followed by post-hoc microarray analysis of tumor tissues.

Results: Our findings revealed that EGFL7 expression was significantly higher in both serum and tumor tissues of mCRPC patients compared to those with BPH or localized PCa. ICAM-1 levels were inversely correlated with EGFL7 expression. Knockdown of EGFL7 in DU145 cells suppressed cell proliferation, migration, and invasion, while in vivo studies demonstrated that EGFL7 silencing inhibited tumor growth and increased ICAM-1 expression along with CD4/8 lymphocyte infiltration. Conversely, overexpression of EGFL7 in PC3 cells promoted tumor progression and reduced ICAM-1 levels.

Conclusions: These findings suggest that EGFL7 overexpression in mCRPC suppresses immune cell infiltration by downregulating endothelial ICAM-1. Our study highlights the potential of EGFL7 as a therapeutic target in advanced PCa.