Time-Dependent Internalization of S100B by Mesenchymal Stem Cells via the Pathways of Clathrin- and Lipid Raft-Mediated Endocytosis

作者全名："Zhang, Ying; Zhu, Jing; Xu, Hao; Yi, Qin; Yan, Liang; Ye, Liang; Zhang, Xinyuan; Xie, Min; Tan, Bin"

作者地址："[Zhang, Ying; Zhu, Jing; Xu, Hao; Yi, Qin; Yan, Liang; Ye, Liang; Zhang, Xinyuan; Xie, Min; Tan, Bin] Chongqing Med Univ, Dept Pediat Res Inst, Childrens Hosp, Chongqing, Peoples R China; [Zhang, Ying; Zhu, Jing; Xu, Hao; Yi, Qin; Yan, Liang; Ye, Liang; Zhang, Xinyuan; Xie, Min; Tan, Bin] Natl Clin Res Ctr Child Hlth & Disorders, Chongqing, Peoples R China; [Zhang, Ying; Zhu, Jing; Xu, Hao; Yi, Qin; Yan, Liang; Ye, Liang; Zhang, Xinyuan; Xie, Min; Tan, Bin] Minist Educ, Key Lab Child Dev & Disorders, Chongqing, Peoples R China; [Zhang, Ying; Zhu, Jing; Xu, Hao; Yi, Qin; Yan, Liang; Ye, Liang; Zhang, Xinyuan; Xie, Min; Tan, Bin] Chongqing Key Lab Pediat, Chongqing, Peoples R China; [Xu, Hao] Chongqing Med Univ, Dept Clin Lab, Childrens Hosp, Chongqing, Peoples R China"

通信作者："Tan, B (corresponding author), Chongqing Med Univ, Dept Pediat Res Inst, Childrens Hosp, Chongqing, Peoples R China.; Tan, B (corresponding author), Natl Clin Res Ctr Child Hlth & Disorders, Chongqing, Peoples R China.; Tan, B (corresponding author), Minist Educ, Key Lab Child Dev & Disorders, Chongqing, Peoples R China.; Tan, B (corresponding author), Chongqing Key Lab Pediat, Chongqing, Peoples R China."

来源：FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000683063600001

JCR分区：Q1

影响因子：5.5

年份：2021

卷号：9

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：MSCs; S100B; glioma microenvironment; internalization; clathrin-mediated endocytosis; clathrin; dynamin; lipid rafts

摘要："Mesenchymal stem cells (MSCs) are promising tools for cancer therapy, but there is a risk of malignant transformation in their clinical application. Our previous work revealed that the paracrine protein S100B in the glioma microenvironment induces malignant transformation of MSCs and upregulates intracellular S100B, which could affect cell homeostasis by interfering with p53. The purpose of this study was to investigate whether extracellular S100B can be internalized by MSCs and the specific endocytic pathway involved in S100B internalization. By using real-time confocal microscopy and structured illumination microscopy (SIM), we visualized the uptake of fluorescently labeled S100B protein (S100B-Alexa488) and monitored the intracellular trafficking of internalized vesicles. The results showed that S100B-Alexa488 was efficiently internalized into MSCs in a time-dependent manner and transported through endolysosomal pathways. After that, we used chemical inhibitors and RNA interference approaches to investigate possible mechanisms involved in S100B-Alexa488 uptake. The internalization of S100B-Alexa488 was inhibited by pitstop-2 or dyngo-4a treatment or RNA-mediated silencing of clathrin or dynamin, and the lipid raft-mediated endocytosis inhibitors nystatin and M beta CD. In conclusion, our findings show that clathrin and lipid rafts contribute to the internalization of S100B-Alexa488, which provides promising interventions for the safe application of MSCs in glioma therapy."

基金机构："Chongqing Science and Technology CommissionNatural Science Foundation Project of CQ CSTC [cstc2017shmsA130019, cstc2020jcyj-msxmX0363]"

基金资助正文：This study was supported by the Chongqing Science and Technology Commission (Grant Numbers cstc2017shmsA130019 and cstc2020jcyj-msxmX0363).