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Establishment of primary cell culture and an intracranial xenograft model of pediatric ependymoma: a prospect for therapy development and understanding of tumor biology
BACKGROUND: Ependymoma (EPN), the third most common pediatric brain tumor, is a central nervous system (CNS) malignancy originating from the walls of the ventricular system. Surgical resection followed by radiation therapy has been the primary treatment for most pediatric intracranial EPNs. Despite...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5955158/ https://www.ncbi.nlm.nih.gov/pubmed/29774098 http://dx.doi.org/10.18632/oncotarget.24932 |
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author | Pavon, Lorena Favaro Sibov, Tatiana Tais Caminada de Toledo, Silvia Regina Mara de Oliveira, Daniela Cabral, Francisco Romero Gabriel de Souza, Jean Boufleur, Pamela Marti, Luciana C. Malheiros, Jackeline Moraes Ferreira da Cruz, Edgar Paiva, Fernando F. Malheiros, Suzana M.F. de Paiva Neto, Manoel A. Tannús, Alberto Mascarenhas de Oliveira, Sérgio Silva, Nasjla Saba Cappellano, Andrea Maria Petrilli, Antonio Sérgio Chudzinski-Tavassi, Ana Marisa Cavalheiro, Sérgio |
author_facet | Pavon, Lorena Favaro Sibov, Tatiana Tais Caminada de Toledo, Silvia Regina Mara de Oliveira, Daniela Cabral, Francisco Romero Gabriel de Souza, Jean Boufleur, Pamela Marti, Luciana C. Malheiros, Jackeline Moraes Ferreira da Cruz, Edgar Paiva, Fernando F. Malheiros, Suzana M.F. de Paiva Neto, Manoel A. Tannús, Alberto Mascarenhas de Oliveira, Sérgio Silva, Nasjla Saba Cappellano, Andrea Maria Petrilli, Antonio Sérgio Chudzinski-Tavassi, Ana Marisa Cavalheiro, Sérgio |
author_sort | Pavon, Lorena Favaro |
collection | PubMed |
description | BACKGROUND: Ependymoma (EPN), the third most common pediatric brain tumor, is a central nervous system (CNS) malignancy originating from the walls of the ventricular system. Surgical resection followed by radiation therapy has been the primary treatment for most pediatric intracranial EPNs. Despite numerous studies into the prognostic value of histological classification, the extent of surgical resection and adjuvant radiotherapy, there have been relatively few studies into the molecular and cellular biology of EPNs. RESULTS: We elucidated the ultrastructure of the cultured EPN cells and characterized their profile of immunophenotypic pluripotency markers (CD133, CD90, SSEA-3, CXCR4). We established an experimental EPN model by the intracerebroventricular infusion of EPN cells labeled with multimodal iron oxide nanoparticles (MION), thereby generating a tumor and providing a clinically relevant animal model. MRI analysis was shown to be a valuable tool when combined with effective MION labeling techniques to accompany EPN growth. CONCLUSIONS: We demonstrated that GFAP/CD133+CD90+/CD44+ EPN cells maintained key histopathological and growth characteristics of the original patient tumor. The characterization of EPN cells and the experimental model could facilitate biological studies and preclinical drug screening for pediatric EPNs. METHODS: In this work, we established notoriously challenging primary cell culture of anaplastic EPNs (WHO grade III) localized in the posterior fossa (PF), using EPNs obtained from 1 to 10-year-old patients (n = 07), and then characterized their immunophenotype and ultrastructure to finally develop a xenograft model. |
format | Online Article Text |
id | pubmed-5955158 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-59551582018-05-17 Establishment of primary cell culture and an intracranial xenograft model of pediatric ependymoma: a prospect for therapy development and understanding of tumor biology Pavon, Lorena Favaro Sibov, Tatiana Tais Caminada de Toledo, Silvia Regina Mara de Oliveira, Daniela Cabral, Francisco Romero Gabriel de Souza, Jean Boufleur, Pamela Marti, Luciana C. Malheiros, Jackeline Moraes Ferreira da Cruz, Edgar Paiva, Fernando F. Malheiros, Suzana M.F. de Paiva Neto, Manoel A. Tannús, Alberto Mascarenhas de Oliveira, Sérgio Silva, Nasjla Saba Cappellano, Andrea Maria Petrilli, Antonio Sérgio Chudzinski-Tavassi, Ana Marisa Cavalheiro, Sérgio Oncotarget Research Paper BACKGROUND: Ependymoma (EPN), the third most common pediatric brain tumor, is a central nervous system (CNS) malignancy originating from the walls of the ventricular system. Surgical resection followed by radiation therapy has been the primary treatment for most pediatric intracranial EPNs. Despite numerous studies into the prognostic value of histological classification, the extent of surgical resection and adjuvant radiotherapy, there have been relatively few studies into the molecular and cellular biology of EPNs. RESULTS: We elucidated the ultrastructure of the cultured EPN cells and characterized their profile of immunophenotypic pluripotency markers (CD133, CD90, SSEA-3, CXCR4). We established an experimental EPN model by the intracerebroventricular infusion of EPN cells labeled with multimodal iron oxide nanoparticles (MION), thereby generating a tumor and providing a clinically relevant animal model. MRI analysis was shown to be a valuable tool when combined with effective MION labeling techniques to accompany EPN growth. CONCLUSIONS: We demonstrated that GFAP/CD133+CD90+/CD44+ EPN cells maintained key histopathological and growth characteristics of the original patient tumor. The characterization of EPN cells and the experimental model could facilitate biological studies and preclinical drug screening for pediatric EPNs. METHODS: In this work, we established notoriously challenging primary cell culture of anaplastic EPNs (WHO grade III) localized in the posterior fossa (PF), using EPNs obtained from 1 to 10-year-old patients (n = 07), and then characterized their immunophenotype and ultrastructure to finally develop a xenograft model. Impact Journals LLC 2018-04-24 /pmc/articles/PMC5955158/ /pubmed/29774098 http://dx.doi.org/10.18632/oncotarget.24932 Text en Copyright: © 2018 Pavon et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Pavon, Lorena Favaro Sibov, Tatiana Tais Caminada de Toledo, Silvia Regina Mara de Oliveira, Daniela Cabral, Francisco Romero Gabriel de Souza, Jean Boufleur, Pamela Marti, Luciana C. Malheiros, Jackeline Moraes Ferreira da Cruz, Edgar Paiva, Fernando F. Malheiros, Suzana M.F. de Paiva Neto, Manoel A. Tannús, Alberto Mascarenhas de Oliveira, Sérgio Silva, Nasjla Saba Cappellano, Andrea Maria Petrilli, Antonio Sérgio Chudzinski-Tavassi, Ana Marisa Cavalheiro, Sérgio Establishment of primary cell culture and an intracranial xenograft model of pediatric ependymoma: a prospect for therapy development and understanding of tumor biology |
title | Establishment of primary cell culture and an intracranial xenograft model of pediatric ependymoma: a prospect for therapy development and understanding of tumor biology |
title_full | Establishment of primary cell culture and an intracranial xenograft model of pediatric ependymoma: a prospect for therapy development and understanding of tumor biology |
title_fullStr | Establishment of primary cell culture and an intracranial xenograft model of pediatric ependymoma: a prospect for therapy development and understanding of tumor biology |
title_full_unstemmed | Establishment of primary cell culture and an intracranial xenograft model of pediatric ependymoma: a prospect for therapy development and understanding of tumor biology |
title_short | Establishment of primary cell culture and an intracranial xenograft model of pediatric ependymoma: a prospect for therapy development and understanding of tumor biology |
title_sort | establishment of primary cell culture and an intracranial xenograft model of pediatric ependymoma: a prospect for therapy development and understanding of tumor biology |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5955158/ https://www.ncbi.nlm.nih.gov/pubmed/29774098 http://dx.doi.org/10.18632/oncotarget.24932 |
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