RUNX3 expression is lost in glioma and its restoration causes drastic suppression of tumor invasion and migration

RUNX3 expression is lost in glioma and its restoration causes drastic suppression of tumor invasion and migration
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RUNX3表达在神经胶质瘤中丢失,其恢复导致肿瘤侵袭和迁移的急剧抑制

DOI:
10.1007/s00432-011-1063-4
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发表时间:
2011-12-01
影响因子:
3.6
通讯作者:
Zheng, Jun-Nian
Zheng, Jun-Nian
中科院分区:
医学3区
文献类型:
--
作者:
Mei, Peng-Jin;Bai, Jin;Zheng, Jun-Nian

文献摘要

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目的探讨RUNX 3蛋白的表达与胶质瘤的发生、发展的关系,以及RUNX 3在胶质瘤细胞生长、侵袭和迁移中的作用。方法采用组织芯片技术,采用免疫组织化学方法检测188例胶质瘤组织、8例正常脑组织和8例癌旁正常脑组织中RUNX 3蛋白的表达。我们通过MTT细胞增殖实验、Matrigel细胞侵袭实验、创伤愈合实验和迁移实验研究RUNX 3修复是否能抑制胶质瘤细胞的生长、侵袭和迁移。结果RUNX 3在良、恶性脑肿瘤组织中的表达均低于瘤旁正常脑组织(P< 0.01和P < 0.05);我们没有发现RUNX 3表达与临床病理参数之间的任何相关性。此外,我们证明了在胶质瘤细胞中重新表达RUNX 3导致显著抑制细胞侵袭和迁移能力。这降低了细胞的侵袭和迁移能力是由于MMP-2蛋白的表达和酶活性抑制后RUNX 3 restoration.ConclusionsOur数据表明,RUNX 3的表达显着降低,在人脑胶质瘤,靶向的RUNX 3通路可能构成一个潜在的治疗方式为胶质瘤。
PurposeThe aim of this study is to investigate whether the expression of RUNX3 is related to the development of glioma, and the role of RUNX3 in glioma cells growth, invasion and migration.MethodsWe analyzed the protein expression of RUNX3 by immunohistochemistry in 188 glioma tissues, 8 normal brain tissues and 8 tumor adjacent normal brain tissues using tissue microarray technique. We studied whether RUNX3 restoration can suppress glioma cells growth, invasion and migration by performing MTT cell proliferation assay, matrigel cell invasion assay, wound-healing assay and migration assay. We also detected MMP-2 protein expression and enzyme activity by western blot analysis and gelatin zymography.ResultsWe found that RUNX3 expression was decreased in benign tumor and malignant tumor compared with tumor adjacent normal brain tissue (P< 0.01 andP< 0.05, respectively). We did not find any correlation between RUNX3 expression and clinicopathological parameters. In addition, we demonstrated that re-expression of RUNX3 in glioma cells resulted in significantly inhibited cell invasion and migration abilities. This reduced cell invasion and migration abilities were due to MMP-2 protein expression and enzyme activity suppression after RUNX3 restoration.ConclusionsOur data indicated that RUNX3 expression is significantly decreased in human glioma, and targeting of the RUNX3 pathway may constitute a potential treatment modality for glioma.