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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显著抑制。

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

机构信息

Department of Neurosurgery, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu Province, China.

出版信息

J Cancer Res Clin Oncol. 2011 Dec;137(12):1823-30. doi: 10.1007/s00432-011-1063-4. Epub 2011 Sep 16.

Abstract

PURPOSE

The 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.

METHODS

We 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.

RESULTS

We found that RUNX3 expression was decreased in benign tumor and malignant tumor compared with tumor adjacent normal brain tissue (P < 0.01 and P < 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.

CONCLUSIONS

Our 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.

摘要

目的

本研究旨在探讨 RUNX3 的表达与胶质瘤的发生发展的关系,以及 RUNX3 在胶质瘤细胞生长、侵袭和迁移中的作用。

方法

我们采用组织微阵列技术,对 188 例胶质瘤组织、8 例正常脑组织和 8 例肿瘤旁正常脑组织进行了 RUNX3 蛋白表达的免疫组化分析。我们通过 MTT 细胞增殖实验、基质胶细胞侵袭实验、划痕愈合实验和迁移实验,研究了 RUNX3 恢复能否抑制胶质瘤细胞的生长、侵袭和迁移。我们还通过 Western blot 分析和明胶酶谱法检测了 MMP-2 蛋白表达和酶活性。

结果

我们发现良性肿瘤和恶性肿瘤中 RUNX3 的表达均低于肿瘤旁正常脑组织(P<0.01 和 P<0.05)。我们没有发现 RUNX3 表达与临床病理参数之间的相关性。此外,我们证明在胶质瘤细胞中重新表达 RUNX3 可显著抑制细胞侵袭和迁移能力。这种降低的细胞侵袭和迁移能力是由于 RUNX3 恢复后 MMP-2 蛋白表达和酶活性的抑制。

结论

我们的数据表明,RUNX3 在人胶质瘤中表达明显下调,靶向 RUNX3 通路可能成为治疗胶质瘤的一种潜在方法。

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