AZGP1 deficiency promotes angiogenesis in prostate cancer

• DOI: 10.1186/s12967-024-05183-x
• Publication Date: 2024-04-24T13:02:31Z
• Authors: Ru M. Wen; Zhengyuan Qiu; G. Edward W. Marti; Eric E. Peterson; Fernando Jose Gar...; Abel Bermudez; Yi Wei; Rosalie Nolley; Nathan Lam; Alex LaPat Polasko; Chun-Lung Chiu; Dalin Zhang; Sanghee Cho; Grigorios Marios ...; Elizabeth McDonough; Chrystal Chadwick; Fiona Ginty; Kyeong Joo Jung; Raghu Machiraju; Parag Mallick; Laura Crowley; Jonathan R. Pollack; Hongjuan Zhao; Sharon J. Pitteri; James D. Brooks
• Keywords: DU145

Abstract Background Loss of AZGP1 expression is a biomarker associated with progression to castration resistance, development metastasis, and poor disease-specific survival in prostate cancer. However, high cells cancer has been reported increase proliferation invasion. The exact role remains elusive. Method knockout overexpressing were generated using lentiviral system. effects under- or over-expression evaluated by vitro cell proliferation, migration, invasion assays. Heterozygous ± mice obtained from European Mouse Mutant Archive (EMMA), tissues homozygous male collected at 2, 6 10 months for histological analysis. In vivo xenografts over-expressing used determine the tumor growth, subsequent proteomics analysis was conducted elucidate mechanisms action progression. microvessel density measured human samples on tissue microarray 215 independent patient samples. Result Neither nor overexpression exhibited significant clonal vitro. prostates −/− initially appeared have grossly normal morphology; however, we observed fibrosis periglandular stroma higher blood vessel mouse months. PC3 DU145 xenografts, did not affect growth. Instead, these tumors displayed decreased compared derived control cells, suggesting that functions inhibit angiogenesis Proteomics profiling further indicated that, are enriched pathway proteins, including YWHAZ, EPHA2, SERPINE1, PDCD6, MMP9, GPX1, HSPB1, COL18A1, RNH1, ANXA1. functional studies show inhibits umbilical vein endothelial tubular formation branching. Additionally, shows negatively correlated tissues. Conclusion negative regulator angiogenesis, such loss promotes likely exerts heterotypical microenvironment, as stromal cells. This study sheds light anti-angiogenic characteristics provides rationale target