Coexpression Of EphrinB2/EphB4 In Human Brain Glioma And Their Biological Significance

Purpose: Gliomas are the most common primary neuroepithelial tumors that are incurable and carry a short survival despite combined therapy including surgery, radiation, and chemotherapy et al. Identifying factors that regulate the growth of glioma would guide the development of novel diagnostic, prognostic and therapeutic targets. Eph receptor tyrosine kinases and their cell-surface-bound ligands, the ephrins, play key roles in diverse biological processes. Originally identified as neuronal path finding molecules, EphB receptors and ephrinB ligands are subsequently proved to be crucial regulators of angiogenesis and embryogenesis. Recent studies have demonstrated that specific Eph receptors are involved in tumorigenesis and neoangiogenesis. But their role in human gliomas is still largely unknown. This study was design to investigate the expression of ephrinB2 and EphB4 in nomal brain tissues and gliomas.Methods: Semi-quantitative RT-PCR and immunohistochemistry were used to examine the expression patterns of ephrinB2 and EphB4. Clinicopathological correlations were statistically analyzed in a series of 32 gliomas and 3 nomal brain specimens.Results: ephrinB2 protein, EphB4 mRNA and EphB4 protein were overexpessed in the majority of tumor tissues and no expression was observed in nomal brain tissues. But ephrinB2 mRNA was highly expressed in all gliomas and normal brain tissues. In addition, a strong immunohistochemical staining for both ephrinB2 and EphB4 was seen in endothelial cells of tumors. Increased ephrinB2 protein, EphB4 mRNA and EphB4 protein expression were positively associated with histological grade although significant correlation with gender and age was not found. There was no correlation between ephrinB2 mRNA expression and histological grade, gender, age. Conclusions: These findings indicate that coexpression of EphB4 and ephrinB2 are involved in the development of glioma and may play dual effects on tumor andneoangiogenesis. Further studies are necessary to determine the functional role ofephrinB2/EphB4 in glioma angiogenesis and growth.