Time-Dependent Internalization of S100B by Mesenchymal Stem Cells via the Pathways of Clathrin- and Lipid Raft-Mediated Endocytosis
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 int...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-07-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.674995/full |
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| author | 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 |
| author_facet | 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 |
| author_sort | Ying Zhang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T10:37:46Z |
| format | Article |
| id | doaj.art-23426c58d48f46b79a0bd495b5a15b5b |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-22T10:37:46Z |
| publishDate | 2021-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-23426c58d48f46b79a0bd495b5a15b5b2022-12-21T18:29:07ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-07-01910.3389/fcell.2021.674995674995Time-Dependent Internalization of S100B by Mesenchymal Stem Cells via the Pathways of Clathrin- and Lipid Raft-Mediated EndocytosisYing Zhang0Ying Zhang1Ying Zhang2Ying Zhang3Jing Zhu4Jing Zhu5Jing Zhu6Jing Zhu7Hao Xu8Hao Xu9Hao Xu10Hao Xu11Qin Yi12Qin Yi13Qin Yi14Qin Yi15Liang Yan16Liang Yan17Liang Yan18Liang Yan19Liang Ye20Liang Ye21Liang Ye22Liang Ye23Xinyuan Zhang24Xinyuan Zhang25Xinyuan Zhang26Xinyuan Zhang27Min Xie28Min Xie29Min Xie30Min Xie31Bin Tan32Bin Tan33Bin Tan34Bin Tan35Department of Pediatric Research Institute, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Chongqing, ChinaMinistry of Education Key Laboratory of Child Development and Disorders, Chongqing, ChinaChongqing Key Laboratory of Pediatrics, Chongqing, ChinaDepartment of Pediatric Research Institute, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Chongqing, ChinaMinistry of Education Key Laboratory of Child Development and Disorders, Chongqing, ChinaChongqing Key Laboratory of Pediatrics, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Chongqing, ChinaMinistry of Education Key Laboratory of Child Development and Disorders, Chongqing, ChinaChongqing Key Laboratory of Pediatrics, Chongqing, ChinaDepartment of Clinical Laboratory, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Pediatric Research Institute, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Chongqing, ChinaMinistry of Education Key Laboratory of Child Development and Disorders, Chongqing, ChinaChongqing Key Laboratory of Pediatrics, Chongqing, ChinaDepartment of Pediatric Research Institute, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Chongqing, ChinaMinistry of Education Key Laboratory of Child Development and Disorders, Chongqing, ChinaChongqing Key Laboratory of Pediatrics, Chongqing, ChinaDepartment of Pediatric Research Institute, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Chongqing, ChinaMinistry of Education Key Laboratory of Child Development and Disorders, Chongqing, ChinaChongqing Key Laboratory of Pediatrics, Chongqing, ChinaDepartment of Pediatric Research Institute, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Chongqing, ChinaMinistry of Education Key Laboratory of Child Development and Disorders, Chongqing, ChinaChongqing Key Laboratory of Pediatrics, Chongqing, ChinaDepartment of Pediatric Research Institute, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Chongqing, ChinaMinistry of Education Key Laboratory of Child Development and Disorders, Chongqing, ChinaChongqing Key Laboratory of Pediatrics, Chongqing, ChinaDepartment of Pediatric Research Institute, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Chongqing, ChinaMinistry of Education Key Laboratory of Child Development and Disorders, Chongqing, ChinaChongqing Key Laboratory of Pediatrics, Chongqing, ChinaMesenchymal 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.https://www.frontiersin.org/articles/10.3389/fcell.2021.674995/fullMSCsS100Bglioma microenvironmentinternalizationclathrin-mediated endocytosisclathrin |
| spellingShingle | 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 Time-Dependent Internalization of S100B by Mesenchymal Stem Cells via the Pathways of Clathrin- and Lipid Raft-Mediated Endocytosis Frontiers in Cell and Developmental Biology MSCs S100B glioma microenvironment internalization clathrin-mediated endocytosis clathrin |
| title | Time-Dependent Internalization of S100B by Mesenchymal Stem Cells via the Pathways of Clathrin- and Lipid Raft-Mediated Endocytosis |
| title_full | Time-Dependent Internalization of S100B by Mesenchymal Stem Cells via the Pathways of Clathrin- and Lipid Raft-Mediated Endocytosis |
| title_fullStr | Time-Dependent Internalization of S100B by Mesenchymal Stem Cells via the Pathways of Clathrin- and Lipid Raft-Mediated Endocytosis |
| title_full_unstemmed | Time-Dependent Internalization of S100B by Mesenchymal Stem Cells via the Pathways of Clathrin- and Lipid Raft-Mediated Endocytosis |
| title_short | Time-Dependent Internalization of S100B by Mesenchymal Stem Cells via the Pathways of Clathrin- and Lipid Raft-Mediated Endocytosis |
| title_sort | time dependent internalization of s100b by mesenchymal stem cells via the pathways of clathrin and lipid raft mediated endocytosis |
| topic | MSCs S100B glioma microenvironment internalization clathrin-mediated endocytosis clathrin |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.674995/full |
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