EBV-Induced CXCL8 Upregulation Promotes Vasculogenic Mimicry in Gastric Carcinoma via NF-κB Signaling

Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) is a distinct entity with a conspicuous tumor microenvironment compared with EBV-negative gastric carcinoma. However, the exact role of EBV in gastric carcinogenesis remains elusive. In the present study, we found that EBV upregulated CXCL8 expression, and CXCL8 significantly promoted vasculogenic mimicry (VM) formation of gastric carcinoma (GC) cells. In accordance with these observations, overexpression of CXCL8 increased cell proliferation and migration of AGS and BGC823 cells, while knockdown of CXCL8 with siRNA inhibited cell proliferation and migration of AGS-EBV cells. In addition, activation of NF-kappa B signaling was involved in VM formation induced by CXCL8, which was blocked by NF-kappa B inhibitors BAY 11-7082 and BMS345541. Furthermore, EBV-encoded lncRNA RPMS1 activated the NF-kappa B signaling cascade, which is responsible for EBV-induced VM formation. Both xenografts and clinical samples of EBVaGC exhibit VM histologically, which are correlated with CXCL8 overexpression. Finally, CXCL8 is positively correlated with overall survival in GC patients. In conclusion, EBV-upregulated CXCL8 expression promotes VM formation in GC via NF-kappa B signaling, and CXCL8 might serve as a novel anti-tumor target for EBVaGC.

Automated summary

This study showed that EBV upregulated CXCL8 expression and promoted VM formation in gastric carcinoma cells. Overexpression of CXCL8 increased cell proliferation and migration, while activation of NF-kappa B signaling was involved in VM formation. EBV-encoded lncRNA RPMS1 also activated the signaling cascade responsible for EBV-induced VM formation.