αvβ3 and αvβ5 integrin expression in glioma periphery

OBJECTIVE: This study analyzed the expression of integrins alphav beta3 and alphav beta5 in glioma tissue and focused on the periphery of high-grade gliomas. METHODS: The analysis was performed with Western blot, immunohistochemistry, and immunofluorescence, by use of two monoclonal antibodies able to recognize the functional integrin heterodimer. The expression of integrin-related ligands and growth factors also was studied. Sections from the tumor periphery were classified as either tumor periphery (light tumor infiltrate or scant visible cells) or peritumor (heavy tumor infiltration). RESULTS: Our data on glioma tissues demonstrated that both integrins were expressed in glioma cells and vasculature and their expression correlated with the histological grade. alphav beta3 expression was prominent in astrocytic tumors. Both integrins were markers of tumor vasculature, particularly of endothelial proliferation. A high-grade glioma periphery demonstrated a prominent expression of integrin alphav beta3. Cells demonstrating alphav beta3 positivity were identified as tumor astrocytes and endothelial cells by double imaging. The same cells were surrounded by some alphav beta3 ligands and co-localized fibroblast growth factor 2. Matrix metalloproteinase 2 also was found to be co-localized with alphav beta3 in the same cells. alphav beta3 expression was more relevant in tumor astrocytes. alphav beta3 integrin and vascular endothelial growth factor expression increased from the periphery to the tumor center. CONCLUSION: Our data support the role of integrins alphav beta3 and alphav beta5 in glioma-associated angiogenesis. In addition, they suggest a role for integrin alphav beta3 in neoangiogenesis and cell migration in high-grade glioma periphery.