Expression of ZEBs in gliomas is associated with invasive properties and histopathological grade.

The invasiveness of glioma cells is the predominant clinical problem associated with this tumor type, and is correlated with pathological malignant grade. ZEB1 is highly expressed in glioma cells and associated with the aggressiveness of various types of cancer. In the present study, the expression of ZEB1 and ZEB2 was examined with the aim of determining the role of ZEBs in glioma. ZEB1 and ZEB2 were highly expressed in all glioma cells used in this study. Double knockdown of ZEB1 and ZEB2 suppressed tumor invasiveness more effectively than knockdown of either alone, in both in vitro and in vivo experiments. ZEB1 and ZEB2 were marginally expressed in grade II, but expressed at higher levels in grade IV. Importantly, ZEB-positive cells were more abundant in recurrent glioma with malignant transformation than in initial grade II tissue from the same case. These results indicate that the levels of ZEB1 and ZEB2 are positively correlated with histopathological grade and invasiveness of glioma, suggesting that δEF1 family proteins (ZEB1 and ZEB2) could be useful as prognostic markers and therapeutic targets in patients with glioma.