Targeting Chondroitin Sulfate Reduces Invasiveness of Glioma Cells by Suppressing CD44 and Integrin beta 1 Expression

doi:10.3390/cells10123594

中山醫學大學機構典藏 CSMUIR > 中山醫學大學研究成果 > 期刊論文 > Item 310902500/23770

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题名:	Targeting Chondroitin Sulfate Reduces Invasiveness of Glioma Cells by Suppressing CD44 and Integrin beta 1 Expression
作者:	Chu, YH;Liao, WC;Ho, YJ;Huang, CH;Tseng, TJ;Liu, CH
关键词:	glioma;chondroitin sulfate;CHSY1;integrin beta 1;CD44;therapeutic peptide
日期:	2021
上传时间:	2022-08-05T09:42:35Z (UTC)
出版者:	MDPI
摘要:	Chondroitin sulfate (CS) is a major component of the extracellular matrix found to be abnormally accumulated in several types of cancer tissues. Previous studies have indicated that CS synthases and modification enzymes are frequently elevated in human gliomas and are associated with poor prognosis. However, the underlying mechanisms of CS in cancer progression and approaches for interrupting its functions in cancer cells remain largely unexplored. Here, we have found that CS was significantly enriched surrounding the vasculature in a subset of glioma tissues, which was akin to the perivascular niche for cancer-initiating cells. Silencing or overexpression of the major CS synthase, chondroitin sulfate synthase 1 (CHSY1), significantly regulated the glioma cell invasive phenotypes and modulated integrin expression. Furthermore, we identified CD44 as a crucial chondroitin sulfate proteoglycan (CSPG) that was modified by CHSY1 on glioma cells, and the suppression of CS formation on CD44 by silencing the CHSY1-inhibited interaction between CD44 and integrin beta 1 on the adhesion complex. Moreover, we tested the CS-specific binding peptide, resulting in the suppression of glioma cell mobility in a fashion similar to that observed upon the silencing of CHSY1. In addition, the peptide demonstrated significant affinity to CD44, promoted CD44 degradation, and suppressed integrin beta 1 expression in glioma cells. Overall, this study proposes a potential regulatory loop between CS, CD44, and integrin beta 1 in glioma cells, and highlights the importance of CS in CD44 stability. Furthermore, the targeting of CS by specific binding peptides has potential as a novel therapeutic strategy for glioma.
URI:	http://dx.doi.org/10.3390/cells10123594 https://www.webofscience.com/wos/woscc/full-record/WOS:000743670600001 https://ir.csmu.edu.tw:8080/handle/310902500/23770
關聯:	CELLS ,2021,v10,issue 12
显示于类别:	[中山醫學大學研究成果] 期刊論文

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