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Tumor Mesenchymal Stromal Cells Regulate Cell Migration of Atypical Teratoid Rhabdoid Tumor through Exosome-Mediated miR155/SMARCA4 Pathway
Atypical teratoid/rhabdoid tumor (ATRT) is a rare pediatric brain tumor with extremely high aggressiveness and poor prognosis. The tumor microenvironment is regulated by a complex interaction among distinct cell types, yet the crosstalk between tumor-associated mesenchymal stem cells (tMSCs) and naï...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563126/ https://www.ncbi.nlm.nih.gov/pubmed/31137686 http://dx.doi.org/10.3390/cancers11050720 |
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author | Yang, Yi-Ping Nguyen, Phan Nguyen Nhi Ma, Hsin-I Ho, Wen-Jin Chen, Yi-Wei Chien, Yueh Yarmishyn, Aliaksandr A. Huang, Pin-I Lo, Wen-Liang Wang, Chien-Ying Liu, Yung-Yang Lee, Yi-Yen Lin, Chien-Min Chen, Ming-Teh Wang, Mong-Lien |
author_facet | Yang, Yi-Ping Nguyen, Phan Nguyen Nhi Ma, Hsin-I Ho, Wen-Jin Chen, Yi-Wei Chien, Yueh Yarmishyn, Aliaksandr A. Huang, Pin-I Lo, Wen-Liang Wang, Chien-Ying Liu, Yung-Yang Lee, Yi-Yen Lin, Chien-Min Chen, Ming-Teh Wang, Mong-Lien |
author_sort | Yang, Yi-Ping |
collection | PubMed |
description | Atypical teratoid/rhabdoid tumor (ATRT) is a rare pediatric brain tumor with extremely high aggressiveness and poor prognosis. The tumor microenvironment is regulated by a complex interaction among distinct cell types, yet the crosstalk between tumor-associated mesenchymal stem cells (tMSCs) and naïve ATRT cells are unclear. In this study, we sought to identify the secretory factor(s) that is responsible for the tMSC-mediated regulation of ATRT migration. Comparing with ATRT cell alone, co-culture of tMSCs or addition of its conditioned medium (tMSC-CM) promoted the migration of ATRT, and this effect could be abrogated by exosome release inhibitor GW4869. The exosomes in tMSC-CM were detected by transmission electron microscope and flow cytometry. ATRT naïve cell-derived conditioned media (ATRT-CM) also enhanced the exosome secretion from tMSCs, indicating the interplay between ATRT cells and tMSCs. Microarray analysis revealed that, compared with that in bone marrow-derived MSCs, microRNA155 is the most upregulated microRNA in the tMSC-CM. Tracing the PK67-labeled exosomes secreted from tMSCs confirmed their incorporation into naïve ATRT cells. After entering ATRT cells, miR155 promoted ATRT cell migration by directly targeting SMARCA4. Knockdown of SMARCA4 mimicked the miR155-driven ATRT cell migration, whereas SMARCA4 overexpression or the delivery of exosomes with miR155 knockdown suppressed the migration. Furthermore, abrogation of exosome release with GW4869 reduced the tumorigenesis of the xenograft containing naïve ATRT cells and tMSCs in immunocompromised recipients. In conclusion, our data have demonstrated that tMSCs secreted miR155-enriched exosomes, and the exosome incorporation and miR155 delivery further promoted migration in ATRT cells via a SMARCA4-dependent mechanism. |
format | Online Article Text |
id | pubmed-6563126 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-65631262019-06-17 Tumor Mesenchymal Stromal Cells Regulate Cell Migration of Atypical Teratoid Rhabdoid Tumor through Exosome-Mediated miR155/SMARCA4 Pathway Yang, Yi-Ping Nguyen, Phan Nguyen Nhi Ma, Hsin-I Ho, Wen-Jin Chen, Yi-Wei Chien, Yueh Yarmishyn, Aliaksandr A. Huang, Pin-I Lo, Wen-Liang Wang, Chien-Ying Liu, Yung-Yang Lee, Yi-Yen Lin, Chien-Min Chen, Ming-Teh Wang, Mong-Lien Cancers (Basel) Article Atypical teratoid/rhabdoid tumor (ATRT) is a rare pediatric brain tumor with extremely high aggressiveness and poor prognosis. The tumor microenvironment is regulated by a complex interaction among distinct cell types, yet the crosstalk between tumor-associated mesenchymal stem cells (tMSCs) and naïve ATRT cells are unclear. In this study, we sought to identify the secretory factor(s) that is responsible for the tMSC-mediated regulation of ATRT migration. Comparing with ATRT cell alone, co-culture of tMSCs or addition of its conditioned medium (tMSC-CM) promoted the migration of ATRT, and this effect could be abrogated by exosome release inhibitor GW4869. The exosomes in tMSC-CM were detected by transmission electron microscope and flow cytometry. ATRT naïve cell-derived conditioned media (ATRT-CM) also enhanced the exosome secretion from tMSCs, indicating the interplay between ATRT cells and tMSCs. Microarray analysis revealed that, compared with that in bone marrow-derived MSCs, microRNA155 is the most upregulated microRNA in the tMSC-CM. Tracing the PK67-labeled exosomes secreted from tMSCs confirmed their incorporation into naïve ATRT cells. After entering ATRT cells, miR155 promoted ATRT cell migration by directly targeting SMARCA4. Knockdown of SMARCA4 mimicked the miR155-driven ATRT cell migration, whereas SMARCA4 overexpression or the delivery of exosomes with miR155 knockdown suppressed the migration. Furthermore, abrogation of exosome release with GW4869 reduced the tumorigenesis of the xenograft containing naïve ATRT cells and tMSCs in immunocompromised recipients. In conclusion, our data have demonstrated that tMSCs secreted miR155-enriched exosomes, and the exosome incorporation and miR155 delivery further promoted migration in ATRT cells via a SMARCA4-dependent mechanism. MDPI 2019-05-24 /pmc/articles/PMC6563126/ /pubmed/31137686 http://dx.doi.org/10.3390/cancers11050720 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Yang, Yi-Ping Nguyen, Phan Nguyen Nhi Ma, Hsin-I Ho, Wen-Jin Chen, Yi-Wei Chien, Yueh Yarmishyn, Aliaksandr A. Huang, Pin-I Lo, Wen-Liang Wang, Chien-Ying Liu, Yung-Yang Lee, Yi-Yen Lin, Chien-Min Chen, Ming-Teh Wang, Mong-Lien Tumor Mesenchymal Stromal Cells Regulate Cell Migration of Atypical Teratoid Rhabdoid Tumor through Exosome-Mediated miR155/SMARCA4 Pathway |
title | Tumor Mesenchymal Stromal Cells Regulate Cell Migration of Atypical Teratoid Rhabdoid Tumor through Exosome-Mediated miR155/SMARCA4 Pathway |
title_full | Tumor Mesenchymal Stromal Cells Regulate Cell Migration of Atypical Teratoid Rhabdoid Tumor through Exosome-Mediated miR155/SMARCA4 Pathway |
title_fullStr | Tumor Mesenchymal Stromal Cells Regulate Cell Migration of Atypical Teratoid Rhabdoid Tumor through Exosome-Mediated miR155/SMARCA4 Pathway |
title_full_unstemmed | Tumor Mesenchymal Stromal Cells Regulate Cell Migration of Atypical Teratoid Rhabdoid Tumor through Exosome-Mediated miR155/SMARCA4 Pathway |
title_short | Tumor Mesenchymal Stromal Cells Regulate Cell Migration of Atypical Teratoid Rhabdoid Tumor through Exosome-Mediated miR155/SMARCA4 Pathway |
title_sort | tumor mesenchymal stromal cells regulate cell migration of atypical teratoid rhabdoid tumor through exosome-mediated mir155/smarca4 pathway |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563126/ https://www.ncbi.nlm.nih.gov/pubmed/31137686 http://dx.doi.org/10.3390/cancers11050720 |
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