CD40 is a regulator for vascular endothelial growth factor in the tumor microenvironment of glioma

CD40 is expressed in many tumor cells, however, its role in tumor biology is yet to be demonstrated. In the present study, we investigated the role of CD40 in gliomas. In vivo, we evaluated CD40 expression in 95 glioma tissues and 10 non-tumorous brain tissues and investigated the relationship between histopathological parameters, vascular density, and vascular endothelial growth factor (VEGF) expressions. In vitro, we aimed to understand the biological relevance of CD40 and VEGF in glioma cell lines. The results clearly demonstrated that CD40 expression, including membranous and cytoplasmic staining, was significantly higher in poorly differentiated and well differentiated gliomas than in the non-tumorous brain tissues (P=0.045 and P=0.043, respectively). In gliomas, the expression of CD40 was significantly correlated with tumor size, VEGF expressions and microvessel density (MVD) (P=0.022, P=0.023 and P=0.0316, respectively). In the in vitro study, stimulation of human glioma cells by CD40 ligation induced the expression and secretion of VEGF and was blocked by anti-CD40 monoclonal antibody. These observations provide evidence that CD40 ligation supports the expression and secretion of VEGF and may be involved in neovascularization of gliomas, they also suggest that CD40 and VEGF may be useful biomarkers for evaluating the risk of developing gliomas, and may also be used as a target for therapy. Crown Copyright (C) 2009 Published by Elsevier B.V. All rights reserved.