Frontiers in Cell and Developmental Biology (Jul 2021)
Time-Dependent Internalization of S100B by Mesenchymal Stem Cells via the Pathways of Clathrin- and Lipid Raft-Mediated Endocytosis
- Ying Zhang,
- Ying Zhang,
- Ying Zhang,
- Ying Zhang,
- Jing Zhu,
- Jing Zhu,
- Jing Zhu,
- Jing Zhu,
- Hao Xu,
- Hao Xu,
- Hao Xu,
- Hao Xu,
- Qin Yi,
- Qin Yi,
- Qin Yi,
- Qin Yi,
- Liang Yan,
- Liang Yan,
- Liang Yan,
- Liang Yan,
- Liang Ye,
- Liang Ye,
- Liang Ye,
- Liang Ye,
- Xinyuan Zhang,
- Xinyuan Zhang,
- Xinyuan Zhang,
- Xinyuan Zhang,
- Min Xie,
- Min Xie,
- Min Xie,
- Min Xie,
- Bin Tan,
- Bin Tan,
- Bin Tan,
- Bin Tan
Affiliations
- Ying Zhang
- Department of Pediatric Research Institute, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Ying Zhang
- National Clinical Research Center for Child Health and Disorders, Chongqing, China
- Ying Zhang
- Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China
- Ying Zhang
- Chongqing Key Laboratory of Pediatrics, Chongqing, China
- Jing Zhu
- Department of Pediatric Research Institute, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Jing Zhu
- National Clinical Research Center for Child Health and Disorders, Chongqing, China
- Jing Zhu
- Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China
- Jing Zhu
- Chongqing Key Laboratory of Pediatrics, Chongqing, China
- Hao Xu
- National Clinical Research Center for Child Health and Disorders, Chongqing, China
- Hao Xu
- Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China
- Hao Xu
- Chongqing Key Laboratory of Pediatrics, Chongqing, China
- Hao Xu
- Department of Clinical Laboratory, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Qin Yi
- Department of Pediatric Research Institute, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Qin Yi
- National Clinical Research Center for Child Health and Disorders, Chongqing, China
- Qin Yi
- Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China
- Qin Yi
- Chongqing Key Laboratory of Pediatrics, Chongqing, China
- Liang Yan
- Department of Pediatric Research Institute, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Liang Yan
- National Clinical Research Center for Child Health and Disorders, Chongqing, China
- Liang Yan
- Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China
- Liang Yan
- Chongqing Key Laboratory of Pediatrics, Chongqing, China
- Liang Ye
- Department of Pediatric Research Institute, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Liang Ye
- National Clinical Research Center for Child Health and Disorders, Chongqing, China
- Liang Ye
- Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China
- Liang Ye
- Chongqing Key Laboratory of Pediatrics, Chongqing, China
- Xinyuan Zhang
- Department of Pediatric Research Institute, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Xinyuan Zhang
- National Clinical Research Center for Child Health and Disorders, Chongqing, China
- Xinyuan Zhang
- Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China
- Xinyuan Zhang
- Chongqing Key Laboratory of Pediatrics, Chongqing, China
- Min Xie
- Department of Pediatric Research Institute, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Min Xie
- National Clinical Research Center for Child Health and Disorders, Chongqing, China
- Min Xie
- Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China
- Min Xie
- Chongqing Key Laboratory of Pediatrics, Chongqing, China
- Bin Tan
- Department of Pediatric Research Institute, Children’s Hospital of Chongqing Medical University, Chongqing, China
- Bin Tan
- National Clinical Research Center for Child Health and Disorders, Chongqing, China
- Bin Tan
- Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China
- Bin Tan
- Chongqing Key Laboratory of Pediatrics, Chongqing, China
- DOI
- https://doi.org/10.3389/fcell.2021.674995
- Journal volume & issue
-
Vol. 9
Abstract
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 MβCD. 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.
Keywords
