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Syndecan-1对syntenin表达及U251胶质瘤细胞迁移的影响。

Effects of syndecan-1 on the expression of syntenin and the migration of U251 glioma cells.

作者信息

Chen Jun, Tang Jun, Chen Wei, Gao Yang, He Yang, Zhang Qiang, Ran Qishan, Cao Fang, Yao Shengtao

机构信息

Department of Cerebrovascular Disease, The First Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China.

Department of Stroke Unit and Neurosurgery, The First People's Hospital of Zunyi, Zunyi, Guizhou 563000, P.R. China.

出版信息

Oncol Lett. 2017 Dec;14(6):7217-7224. doi: 10.3892/ol.2017.7170. Epub 2017 Oct 11.

Abstract

Glioma is the most frequently occuring primary brain tumor. Syndecan-1 (SDC1) expression is related to poor prognosis of numerous human malignancies including glioma. Syndecan binding protein (SDCBP) is an important partner for SDC1. The present study investigated whether SDC1 and SDCBP are expressed in glioma and their functions on glioma cell migration. An immunohistochemical assay revealed that SDC1 and SDCBP were expressed and were positively related to malignant level of glioma (SDC1, r=0.576, P=0.001; SDCBP, r=0.661, P<0.001). Moreover, the protein levels of SDC1 were positively correlated with those of SDCBP in glioma tissues (r=0.628, P=0.001). In U251 glioma cells, protein levels of SDC1 and SDCBP were both upregulated in U251 cells with SDC1 overexpression, while downregulated with SDC1 knockdown. Transwell assay and scratch-wound healing assay showed that SDC1 overexpression significantly increased U251 cell migration, while SDC1 knockdown had the opposite effects. Rac1 activity, signal transducer and activator of transcription 3 (STAT3) phosphorylation, as well as expression of matrix metalloproteinase 2 (MMP2) and MMP9 was significantly increased by SDC1 overexpression, while was decreased by SDC1 knockdown. In conclusion, SDC1 overexpression upregulated SDCBP expression, and promoted glioma cell migration via Rac1 activation.

摘要

神经胶质瘤是最常见的原发性脑肿瘤。Syndecan-1(SDC1)的表达与包括神经胶质瘤在内的多种人类恶性肿瘤的不良预后相关。Syndecan结合蛋白(SDCBP)是SDC1的重要伴侣。本研究调查了SDC1和SDCBP在神经胶质瘤中的表达情况及其对神经胶质瘤细胞迁移的作用。免疫组织化学分析显示,SDC1和SDCBP均有表达,且与神经胶质瘤的恶性程度呈正相关(SDC1,r=0.576,P=0.001;SDCBP,r=0.661,P<0.001)。此外,在神经胶质瘤组织中,SDC1的蛋白水平与SDCBP的蛋白水平呈正相关(r=0.628,P=0.001)。在U251神经胶质瘤细胞中,SDC1过表达的U251细胞中SDC1和SDCBP的蛋白水平均上调,而SDC1敲低时则下调。Transwell实验和划痕愈合实验表明,SDC1过表达显著增加U251细胞迁移,而SDC1敲低则产生相反的效果。SDC1过表达显著增加了Rac1活性、信号转导和转录激活因子3(STAT3)磷酸化以及基质金属蛋白酶2(MMP2)和MMP9的表达,而SDC1敲低则降低了这些指标。总之,SDC1过表达上调了SDCBP表达,并通过激活Rac1促进神经胶质瘤细胞迁移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c59c/5754878/dcf4d08a5d4d/ol-14-06-7217-g00.jpg

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