Glioblastoma multiforme (GBM) is the most common type of primary brain tumour in adults, and presents a very low survival rate. Isocitrate dehydrogenase (IDH)1/2 mutations have been found in ~12% of glioblastomas and are associated with long‑term GBM survival. However, the risk factors that influence the prognosis of IDH‑wild type GBM remain unclear. Hypoxia‑inducible factor (HIF)‑1α, an important oxygen‑regulated transcription factor, has been demonstrated to serve a crucial role in tumour development and to be associated with a poor prognosis. In addition, caveolin‑1 (CAV1) is a plasma membrane organizing protein, the expression of which can also be regulated by a hypoxic microenvironment. The present study therefore aimed to examine the expression levels of HIF‑1α and CAV1, and their association with GBM prognosis. Reverse transcription‑quantitative polymerase chain reaction and western blotting were performed to analyse the expression levels of HIF‑1α and CAV1 in paired GBM tumour and adjacent non‑tumour tissues. Immunohistochemistry was used to analyse the expression of the two proteins in paraffin‑embedded tissues obtained from 42 patients with IDH‑wild type GBM. Statistical analyses were performed to examine the correlation between HIF‑1α and CAV1 expression and patient prognosis. The results revealed hat the expression levels of HIF‑1α and CAV1 were upregulated in IDH‑wild type GBM tissues compared to their paired non‑tumour tissues (P<0.001). The expression of CAV1 was significantly correlated with high HIF‑1α expression (P<0.01). In addition, overexpression of HIF‑1α and CAV1 was markedly associated with a poor prognosis (P<0.001). In conclusion, HIF‑1α and CAV1 may represent potential biomarkers for IDH‑wild type GBM prognosis and potential targets for the development of therapies extending GBM survival.

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. In this study, we examined CAV-1 expression levels and VM in human glioma cell lines and in 94 human gliomas with different grades of malignancy, and present Cox proportional hazards regression. The molecular role of Cav-1 in glioma cells was investigated using quantitative polymerase chain reaction (qRT-PCR) assays, western blotting, CCK-8 assays, and tubule formation assays. Cav-1 expression and VM formation were positively correlated with each other and both were closely associated with glioma development and progression as evidenced by the presence of cystic tumor, shortened survival time, and advanced-stage glioma in glioma patients with Cav-1 overexpression/increased VM formation. Cav-1 promoted U251 glioma cell proliferation and VM formation in a Matrigel-based 3D culture model. VM-associated factors including hypoxia-inducible factor 1α (HIF-1α) and p-Akt was significantly elevated by Cav-1 overexpression but suppressed by siCav-1 in U251 cells. Collectively, our study identified Cav-1 as an important regulator of glioma cell proliferation and VM formation, contributing to glioma development and progression.

Background: 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 VM 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.

Background: 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, we examined CAV-1 expression levels and vasculogenic mimicry in human glioma cell lines and in 94 human gliomas with different grades and presented cox proportional hazards regression. The molecular role of Cav-1 in glioma cells was investigated using quantitative polymerase chain reaction (qRT-PCR) assays, Western blotting, CCK-8 assays, tubule formation assays. Results: Cav-1 expression and VM 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. Cav-1 promoted U251 glioma cell proliferation and VM formation in a Matrigel-based 3D culture model. VM-associated factors including hypoxia-inducible factor 1α (HIF-1α) and p-Akt was significantly elevated by Cav-1 overexpression but suppressed by siCav-1 in U251 cells. Conclusion: Collectively, our study identifies Cav-1 as an important regulator of glioma cell proliferation and VM formation, contributing to glioma development and progression.