WISP2 Overexpression Is Associated with Reduced Vasculogenic Mimicry and Epithelial–Mesenchymal Transition in Gastric Cancer

To investigate the association between WISP2 overexpression, vasculogenic mimicry (VM), and epithelial–mesenchymal transition (EMT) in gastric cancer. Pathological specimens from 50 patients who underwent radical gastrectomy at the First Affiliated Hospital of Bengbu Medical College between February 2022 and February 2023 were analyzed. WISP2 expression and VM formation in tumor and adjacent tissues were evaluated using GEPIA database analysis and immunohistochemistry. Gastric cancer cell proliferation, migration, and invasion were assessed using CCK-8, scratch wound, and Transwell assays, respectively. Nude mouse xenograft models were established to evaluate tumor growth and VM formation in vivo. The expression of VM- and EMT-related molecules was examined by quantitative PCR and Western blotting. VM structures were observed in gastric cancer tissues, and WISP2 expression was significantly lower in VM-positive specimens compared with VM-negative specimens (P < 0.05). Overexpression of WISP2 significantly inhibited gastric cancer cell proliferation, migration, and invasion (all P < 0.05). Increased WISP2 expression was associated with suppression of EMT features and reduced VM-forming capacity (both P < 0.05). In xenograft models, tumors overexpressing WISP2 showed decreased tumor growth and reduced VM formation compared with controls (P < 0.05). Western blot analysis demonstrated that WISP2 overexpression was associated with downregulation of p-β-catenin (Ser675), total β-catenin, p-GSK-3β (Ser9), and TCF4 (P < 0.05). WISP2 overexpression is associated with reduced vasculogenic mimicry in gastric cancer, potentially through suppression of EMT and inhibition of the Wnt/β-catenin signaling pathway.