Suzuki Keiko, Kawataki Tomoyuki, Endo Kaori, Miyazawa Keiji, Kinouchi Hiroyuki, Saitoh Masao
Department of Neurosurgery, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi 409-3898, Japan.
Department of Biochemistry, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi 409-3898, Japan.
Oncol Lett. 2018 Aug;16(2):1758-1764. doi: 10.3892/ol.2018.8852. Epub 2018 May 31.
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 and 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.
胶质瘤细胞的侵袭性是与这种肿瘤类型相关的主要临床问题，并且与病理恶性程度相关。ZEB1在胶质瘤细胞中高表达，并且与各种类型癌症的侵袭性有关。在本研究中，检测了ZEB1和ZEB2的表达，目的是确定ZEBs在胶质瘤中的作用。在本研究中使用的所有胶质瘤细胞中，ZEB1和ZEB2均高表达。在体外和体内实验中，ZEB1和ZEB2的双敲低比单独敲低更有效地抑制肿瘤侵袭性。ZEB1和ZEB2在二级胶质瘤中表达较少，但在四级胶质瘤中表达较高。重要的是，与同一病例的初始二级组织相比，伴有恶性转化的复发性胶质瘤中ZEB阳性细胞更为丰富。这些结果表明，ZEB1和ZEB2的水平与胶质瘤的组织病理学分级和侵袭性呈正相关，提示δEF1家族蛋白（ZEB1和ZEB2）可作为胶质瘤患者的预后标志物和治疗靶点。
