Human neural stem cells repress glioma cell progression in a paracrine manner by downregulating the Wnt/β-catenin signalling pathway

被引：1

作者：

Yin, Xiaolin ^{[1
]}

Liu, Xiumei ^{[2
]}

Xiao, Xiangyi ^{[1
]}

Yi, Kaiyu ^{[1
]}

Chen, Weigong ^{[2
]}

Han, Chao ^{[1
]}

Wang, Liang ^{[1
]}

Li, Ying ^{[1
,3
,4
]}

Liu, Jing ^{[1
,3
,4
]}

机构：

[1] Dalian Med Univ, Affiliated Hosp 1, Stem Cell Clin Res Ctr, Regenerat Med Ctr,Natl Joint Engn Lab, Dalian, Peoples R China

[2] Dalian Innovat Inst Stem Cell & Precis Med, Dalian, Peoples R China

[3] Dalian Med Univ, Affiliated Hosp 1, Stem Cell Clin Res Ctr, Regenerat Med Ctr,Natl Joint Engn Lab, Dalian 116000, Peoples R China

[4] Dalian Innovat Inst Stem Cell & Precis Med, Dalian 116000, Peoples R China

来源：

FEBS OPEN BIO | 2023年 / 13卷 / 09期

基金：

中国国家自然科学基金;

关键词：

conditioned medium; glioma; human neural stem cells; invasion; proliferation; CONDITIONED MEDIUM; BETA-CATENIN; EXPRESSION; DICKKOPF-1; CARCINOMA; INHIBIT; FOXM1; MET;

D O I：

10.1002/2211-5463.13671

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Neural stem cells (NSCs) play crucial roles in neurological disorders and tissue injury repair through exerting paracrine effects. However, the effects of NSC-derived factors on glioma progression remain unclear. This study aimed to evaluate the effects of human NSC-conditioned medium (NSC-CM) on the behaviour of glioma cells using an in vitro co-culture system. Cell counting kit-8 and 5-ethynyl-2'-deoxyuridine assays revealed that NSC-CM inhibited glioma cell proliferation and growth in a fetal bovine serum (FBS)-independent manner. In addition, our wound-healing assay demonstrated that NSC-CM repressed glioma cell migration, while results from transwell and 3D spheroid invasion assays indicated that NSC-CM also reduced the invasion capacity of glioma cells. Flow cytometry showed that NSC-CM prevented cell cycle progression from the G1 to S phase and promoted apoptosis. Western blotting was used to show that the expression of Wnt/beta-catenin pathway-related proteins, including beta-catenin, c-Myc, cyclin D1, CD44 and Met, was remarkably decreased in NSC-CM-treated glioma cells. Furthermore, the addition of a Wnt/beta-catenin pathway activator, CHIR99021, significantly induced the expression of beta-catenin and Met and increased the proliferative and invasive capabilities of control medium-treated glioma cells but not those of NSC-CM-treated glioma cells. The use of enzyme-linked immunosorbent assays (ELISA) revealed the secretion of some antitumour factors in human and rat NSCs, including interferon-a and dickkopf-1. Our data suggest that NSC-CM partially inhibits glioma cell progression by downregulating Wnt/beta-catenin signalling. This study may serve as a basis for developing future antiglioma therapies based on NSC derivatives.

引用

页码：1772 / 1788

页数：17