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β3GnT8的高表达与人胶质瘤的转移潜能相关。

High expression of β3GnT8 is associated with the metastatic potential of human glioma.

作者信息

Liu Jun, Shen Li, Yang Lingyan, Hu Shuijun, Xu Lan, Wu Shiliang

机构信息

Department of Biochemistry and Molecular Biology, Soochow University, Suzhou, Jiangsu 215123, P.R. China.

出版信息

Int J Mol Med. 2014 Jun;33(6):1459-68. doi: 10.3892/ijmm.2014.1736. Epub 2014 Apr 8.

DOI:10.3892/ijmm.2014.1736
PMID:24715095
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4055349/
Abstract

Changes in glycosylation due to specific alterations of glycosyltransferase activity have been shown in various tumor cells, including human glioma cells. β1,3-N‑acetylglucosaminyltransferase-8 (β3GnT8) catalyzes the formation of polylactosamine on β1-6 branched N-glycans. Upregulated expression of β3GnT8 was described in some tumors, but its precise role in regulating glioma invasion and metastasis remains unclear. In this study, we report on an investigation of the expression of β3GnT8 in human glioma by immunohistochemical analysis. Out of 42 glioma tissues, 37 (88.1%) showed positive β3GnT8 expression, which was significantly higher than that in normal brain tissues (P<0.001). Additionally, the level of β3GnT8 increased with increased pathological grade of gliomas. Silencing of β3GnT8 in U251 glioma cells attenuated the formation of polylactosamine, and decreased cell proliferation, migration and metastatic ability in vitro and in vivo. By contrast, the overexpression of β3GnT8 in U251 cells exhibited enhanced metastatic potential. A positive correlation between β3GnT8 and matrix metalloproteinase-2 (MMP-2) expression in U251 cells was also observed. The results demonstrated a critical role of β3GnT8 in the metastatic potential of glioma cells, indicating that manipulating β3GnT8 expression may have therapeutic potential for the treatment of malignant glioma.

摘要

由于糖基转移酶活性的特定改变而导致的糖基化变化已在包括人类胶质瘤细胞在内的各种肿瘤细胞中得到证实。β1,3-N-乙酰氨基葡萄糖转移酶-8（β3GnT8）催化在β1-6分支的N-聚糖上形成多乳糖胺。在一些肿瘤中描述了β3GnT8表达上调，但其在调节胶质瘤侵袭和转移中的精确作用仍不清楚。在本研究中，我们报告了通过免疫组织化学分析对人类胶质瘤中β3GnT8表达的调查。在42个胶质瘤组织中，37个（88.1%）显示β3GnT8表达阳性，这显著高于正常脑组织（P<0.001）。此外，β3GnT8的水平随着胶质瘤病理分级的增加而升高。在U251胶质瘤细胞中沉默β3GnT8可减弱多乳糖胺的形成，并在体外和体内降低细胞增殖、迁移和转移能力。相比之下，在U251细胞中过表达β3GnT8表现出增强的转移潜力。在U251细胞中还观察到β3GnT8与基质金属蛋白酶-2（MMP-2）表达之间呈正相关。结果表明β3GnT8在胶质瘤细胞的转移潜力中起关键作用，表明操纵β3GnT8表达可能对恶性胶质瘤的治疗具有治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/818c/4055349/3024028f9efb/IJMM-33-06-1459-g07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/818c/4055349/8f4c6c2c098c/IJMM-33-06-1459-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/818c/4055349/46f2f24dbe99/IJMM-33-06-1459-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/818c/4055349/dee44a2bac53/IJMM-33-06-1459-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/818c/4055349/46f75c9ebab3/IJMM-33-06-1459-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/818c/4055349/77c86f6cb0db/IJMM-33-06-1459-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/818c/4055349/5c3d5a33ddec/IJMM-33-06-1459-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/818c/4055349/864387c693cc/IJMM-33-06-1459-g06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/818c/4055349/3024028f9efb/IJMM-33-06-1459-g07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/818c/4055349/8f4c6c2c098c/IJMM-33-06-1459-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/818c/4055349/46f2f24dbe99/IJMM-33-06-1459-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/818c/4055349/dee44a2bac53/IJMM-33-06-1459-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/818c/4055349/46f75c9ebab3/IJMM-33-06-1459-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/818c/4055349/77c86f6cb0db/IJMM-33-06-1459-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/818c/4055349/5c3d5a33ddec/IJMM-33-06-1459-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/818c/4055349/864387c693cc/IJMM-33-06-1459-g06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/818c/4055349/3024028f9efb/IJMM-33-06-1459-g07.jpg

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