Vasculogenic mimicry (VM) plays an important role in human glioma progression and resistance to antiangiogenic therapy as a compensatory neovascularization mechanism in malignant tumors. Caveolin-1 (Cav-1) has been found to contribute to VM formation. However, it remains largely unknown whether Cav-1 expression correlates with VM in glioma. Methods: In this study, by performing immnunohistochemical staining of Cav-1 and CD31/Periodic acid-Schiff co-staining, we found that Cav-1 expression and

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... formation were positively correlated with each other and both are closely associated with glioma development and progression as evidenced by the presence of cystic tumor, the shortened survival time and advanced-stage glioma in glioma patients with Cav-1 overexpression/increased VM formation, suggesting Cav-1 as a prognostic indicator in glioma. Results: Gain-and loss-of-function analyses showed that Cav-1 promoted U251 glioma cell proliferation and VM formation in a Matrigel-based 3D culture model. Mechanistically, overexpression of Cav-1 upregulated while knockdown of Cav-1 downregulated the mRNA/protein expression of VM-associated genes including Akt and hypoxia-inducible factor 1α (HIF-1α), respectively, suggesting that the Akt signaling and HIF-1α may be involved in Cav-1-induced glioma cell proliferation and VM formation. Conclusion: Collectively, our study identifies Cav-1 as an important regulator of glioma cell proliferation and VM formation, contributing to glioma development and progression.