Vasculogenic mimicry formation in EBV-associated epithelial malignancies

Area of Science:

• Oncology
• Virology
• Cancer Biology

Background:

• Epstein-Barr virus (EBV) is linked to epithelial cancers like nasopharyngeal carcinoma (NPC) and EBV-positive gastric cancer (EBVaGC).
• The precise role of EBV in epithelial tumor development remains unclear.
• Vasculogenic mimicry (VM), a tumor angiogenesis mechanism, is observed in various cancers.

Purpose of the Study:

• To investigate the role of EBV in vasculogenic mimicry (VM) in epithelial cancers.
• To elucidate the molecular mechanisms underlying EBV-induced VM.
• To explore potential therapeutic strategies targeting EBV-associated VM.

Main Methods:

• Analysis of EBV-infected epithelial cells and tumor samples (NPC, EBVaGC).
• Histological examination for VM.
• Assessment of signaling pathways including PI3K/AKT/mTOR/HIF-1α and EBV's LMP2A protein.
• Evaluation of anti-cancer effects of monotherapy (anti-VEGF) and combination therapy (VEGF and HIF-1α inhibitors).

Main Results:

• EBV infection induces VM in epithelial cancer cells, forming tumor vascular networks independent of VEGF.
• Activation of the PI3K/AKT/mTOR/HIF-1α pathway, partly mediated by LMP2A, drives EBV-induced VM.
• VM and activation of AKT/HIF-1α were observed in clinical NPC and EBVaGC samples.
• Combination therapy targeting VEGF and HIF-1α showed synergistic antitumor activity.

Conclusions:

• EBV infection confers an endothelial-like phenotype to epithelial cancer cells, promoting VM.
• EBV-induced VM represents a distinct tumor vascularization pathway.
• Targeting EBV-induced VM, particularly through combined VEGF and HIF-1α inhibition, offers a promising therapeutic strategy for EBV-associated epithelial cancers.