New models for MPNST: establishment and comprehensive characterization of two tumor cell lines

Background: Malignant peripheral nerve sheath tumors (MPNSTs) are rare, invasive, and aggressive soft tissue sarcomas arising from peripheral nerves. They may occur sporadically or in association with Neurofibromatosis type 1 (NF1), in which they are the leading cause of mortality. Currently, there...

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Autores: Ortega Bertran, Sara, Creus Bachiller, Edgar, Magallón Lorenz, Miriam, Carrió, Meritxell, Gel Moreno, Bernat, Villanueva Garatachea, Alberto, Lopez-Gutierrez, Juan Carlos, Estival, Anna, Serra, Eduard, Fernández Rodríguez, Juana, Lázaro García, Conxi
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/222881
Acceso en línea:https://hdl.handle.net/2445/222881
Access Level:acceso abierto
Palabra clave:Tumors
Regulació cel·lular
Neurofibromatosi
Cellular control mechanisms
Neurofibromatosis
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spelling New models for MPNST: establishment and comprehensive characterization of two tumor cell linesOrtega Bertran, SaraCreus Bachiller, EdgarMagallón Lorenz, MiriamCarrió, MeritxellGel Moreno, BernatVillanueva Garatachea, AlbertoLopez-Gutierrez, Juan CarlosEstival, AnnaSerra, EduardFernández Rodríguez, JuanaLázaro García, ConxiTumorsRegulació cel·lularNeurofibromatosiTumorsCellular control mechanismsNeurofibromatosisBackground: Malignant peripheral nerve sheath tumors (MPNSTs) are rare, invasive, and aggressive soft tissue sarcomas arising from peripheral nerves. They may occur sporadically or in association with Neurofibromatosis type 1 (NF1), in which they are the leading cause of mortality. Currently, there are no effective therapies other than surgery. Therefore, tumor-derived cell lines are essential for testing new therapeutic strategies, especially when used in parallel with in vivo models. In this study, we present two new MPNST cell lines and two patient-derived orthotopic xenograft (PDOX) models from a sporadic (SP-10) and an NF1-related (NF1-18B) MPNST patient to increase the number of available preclinical models for in vitro and in vivo drug testing. Methods: The cell lines were isolated and extensively characterized genetically (tumor suppressor gene mutation status, DNA content), phenotypically (cell morphology, marker expression), and functionally (proliferation rate, colony formation capacity, migration rate, tumorigenic ability). We validated the models by comparing the genomic (copy number variation profile) and histological characteristics of the cell lines and PDOX tumors with their corresponding patient tumors. Results: The new cell lines and PDOXs tumors exhibited similar genomic copy number variation profiles, histological patterns, and marker expressions as the patient tumors, validating them as faithful models. Interestingly, the NF1-18B cell model presented two cell subpopulations with different ploidy states (one < 3n and the other 4n) and functional features in vitro. NF1-18B 4n, along with SP-10 cell lines, exhibited in vitro functional hallmarks of MPNSTs, including high proliferation and migration rates and colony forming ability. However, only the SP-10 model exhibited aggressive tumorigenicity in athymic mice. In contrast, the NF1-18B < 3n showed a low migration rate and did not form colonies or aggregates in vitro. Conclusions: The newly established MPNST cell lines, along with their corresponding PDOX models, serve as valuable tools for both in vitro and in vivo testing of novel therapeutic agents. Notably, the SP-10 cell line model represents one of the few documented cases isolated from a genuine "classic" MPNST.BioMed Central2025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/222881Articles publicats en revistes (Fonaments Clínics)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1186/s12935-025-03845-4Cancer Cell International, 2025, vol. 25, num.1https://doi.org/10.1186/s12935-025-03845-4cc-by (c) Ortega-Bertran, S. et al., 2025http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2228812026-05-27T06:46:51Z
dc.title.none.fl_str_mv New models for MPNST: establishment and comprehensive characterization of two tumor cell lines
title New models for MPNST: establishment and comprehensive characterization of two tumor cell lines
spellingShingle New models for MPNST: establishment and comprehensive characterization of two tumor cell lines
Ortega Bertran, Sara
Tumors
Regulació cel·lular
Neurofibromatosi
Tumors
Cellular control mechanisms
Neurofibromatosis
title_short New models for MPNST: establishment and comprehensive characterization of two tumor cell lines
title_full New models for MPNST: establishment and comprehensive characterization of two tumor cell lines
title_fullStr New models for MPNST: establishment and comprehensive characterization of two tumor cell lines
title_full_unstemmed New models for MPNST: establishment and comprehensive characterization of two tumor cell lines
title_sort New models for MPNST: establishment and comprehensive characterization of two tumor cell lines
dc.creator.none.fl_str_mv Ortega Bertran, Sara
Creus Bachiller, Edgar
Magallón Lorenz, Miriam
Carrió, Meritxell
Gel Moreno, Bernat
Villanueva Garatachea, Alberto
Lopez-Gutierrez, Juan Carlos
Estival, Anna
Serra, Eduard
Fernández Rodríguez, Juana
Lázaro García, Conxi
author Ortega Bertran, Sara
author_facet Ortega Bertran, Sara
Creus Bachiller, Edgar
Magallón Lorenz, Miriam
Carrió, Meritxell
Gel Moreno, Bernat
Villanueva Garatachea, Alberto
Lopez-Gutierrez, Juan Carlos
Estival, Anna
Serra, Eduard
Fernández Rodríguez, Juana
Lázaro García, Conxi
author_role author
author2 Creus Bachiller, Edgar
Magallón Lorenz, Miriam
Carrió, Meritxell
Gel Moreno, Bernat
Villanueva Garatachea, Alberto
Lopez-Gutierrez, Juan Carlos
Estival, Anna
Serra, Eduard
Fernández Rodríguez, Juana
Lázaro García, Conxi
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Tumors
Regulació cel·lular
Neurofibromatosi
Tumors
Cellular control mechanisms
Neurofibromatosis
topic Tumors
Regulació cel·lular
Neurofibromatosi
Tumors
Cellular control mechanisms
Neurofibromatosis
description Background: Malignant peripheral nerve sheath tumors (MPNSTs) are rare, invasive, and aggressive soft tissue sarcomas arising from peripheral nerves. They may occur sporadically or in association with Neurofibromatosis type 1 (NF1), in which they are the leading cause of mortality. Currently, there are no effective therapies other than surgery. Therefore, tumor-derived cell lines are essential for testing new therapeutic strategies, especially when used in parallel with in vivo models. In this study, we present two new MPNST cell lines and two patient-derived orthotopic xenograft (PDOX) models from a sporadic (SP-10) and an NF1-related (NF1-18B) MPNST patient to increase the number of available preclinical models for in vitro and in vivo drug testing. Methods: The cell lines were isolated and extensively characterized genetically (tumor suppressor gene mutation status, DNA content), phenotypically (cell morphology, marker expression), and functionally (proliferation rate, colony formation capacity, migration rate, tumorigenic ability). We validated the models by comparing the genomic (copy number variation profile) and histological characteristics of the cell lines and PDOX tumors with their corresponding patient tumors. Results: The new cell lines and PDOXs tumors exhibited similar genomic copy number variation profiles, histological patterns, and marker expressions as the patient tumors, validating them as faithful models. Interestingly, the NF1-18B cell model presented two cell subpopulations with different ploidy states (one < 3n and the other 4n) and functional features in vitro. NF1-18B 4n, along with SP-10 cell lines, exhibited in vitro functional hallmarks of MPNSTs, including high proliferation and migration rates and colony forming ability. However, only the SP-10 model exhibited aggressive tumorigenicity in athymic mice. In contrast, the NF1-18B < 3n showed a low migration rate and did not form colonies or aggregates in vitro. Conclusions: The newly established MPNST cell lines, along with their corresponding PDOX models, serve as valuable tools for both in vitro and in vivo testing of novel therapeutic agents. Notably, the SP-10 cell line model represents one of the few documented cases isolated from a genuine "classic" MPNST.
publishDate 2025
dc.date.none.fl_str_mv 2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/222881
url https://hdl.handle.net/2445/222881
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1186/s12935-025-03845-4
Cancer Cell International, 2025, vol. 25, num.1
https://doi.org/10.1186/s12935-025-03845-4
dc.rights.none.fl_str_mv cc-by (c) Ortega-Bertran, S. et al., 2025
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Ortega-Bertran, S. et al., 2025
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv Articles publicats en revistes (Fonaments Clínics)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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