Background/Aim: Glioblastoma is a recalcitrant and poorly understood disease. The aim of the present study was to investigate the effect of moesin up-regulation on tumor progression in an orthotopic nude-mouse model of human glioblastoma. Materials and Methods: U87-GFP glioblastoma cells, transfected with either U87-H4645 (moesin up-regulated) or U87-H149 (vector control) were orthotopically implanted into the brains of nude mice. Moesin expression in the tumors was analyzed with RT-PCR and western blotting. Real-time fluorescence imaging was used to longitudinally and non-invasively quantitate tumor growth. The expression of cancer-related genes β-catenin, CD44, MMP-2, ICAM-1, and PCNA in the tumor was analyzed by RT-PCR, western blotting and immunohistochemistry in both sublines. Results: The expression levels of moesin mRNA and protein were significantly increased in the glioblastoma derived from transfected U87-H4645 cells compared to the vector control and untransfected cells. Tumor growth rate and final tumor weight were significantly increased in the animals with the glioblastoma derived from transfected U87-H4645 cells, compared to untransfected and vector control (p〈0.01). mRNA expression of β-catenin, CD44, ICAM-1, and MMP-2 in the glioblastoma derived from the transfected U87-H4645 tumors was significantly increased compared with tumors derived from untransfected and vector-control U87 cells (p〈0.01). Furthermore, a similar increase in the expression of these proteins was observed by western blotting or immunohistochemistry. Conclusion: Up-regulation of moesin expression in glioblastoma cells resulted in more aggressive orthotopic glioblastoma growth in nude mice. This effect may be mediated by the regulation of several proliferation-, adhesion-, and invasion-related cancer genes, which may serve as future therapeutic targets for this recalcitrant disease.