New models for MPNST: establishment and comprehensive characterization of two tumor cell lines
Abstract 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...
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BMC
2025-07-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-025-03845-4 |
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| author | Sara Ortega-Bertran Edgar Creus-Bachiller Miriam Magallón-Lorenz Meritxell Carrió Bernat Gel Alberto Villanueva Juan Carlos Lopez-Gutierrez Anna Estival Eduard Serra Juana Fernández-Rodríguez Conxi Lázaro |
| author_facet | Sara Ortega-Bertran Edgar Creus-Bachiller Miriam Magallón-Lorenz Meritxell Carrió Bernat Gel Alberto Villanueva Juan Carlos Lopez-Gutierrez Anna Estival Eduard Serra Juana Fernández-Rodríguez Conxi Lázaro |
| author_sort | Sara Ortega-Bertran |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-854a2674800a4e0bb312d389222bd6f5 |
| institution | Kabale University |
| issn | 1475-2867 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
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| series | Cancer Cell International |
| spelling | doaj-art-854a2674800a4e0bb312d389222bd6f52025-08-20T04:03:07ZengBMCCancer Cell International1475-28672025-07-0125111310.1186/s12935-025-03845-4New models for MPNST: establishment and comprehensive characterization of two tumor cell linesSara Ortega-Bertran0Edgar Creus-Bachiller1Miriam Magallón-Lorenz2Meritxell Carrió3Bernat Gel4Alberto Villanueva5Juan Carlos Lopez-Gutierrez6Anna Estival7Eduard Serra8Juana Fernández-Rodríguez9Conxi Lázaro10Hereditary Cancer Program, Catalan Institute of Oncology (ICO-IDIBELL), Hospitalet de LlobregatHereditary Cancer Program, Catalan Institute of Oncology (ICO-IDIBELL), Hospitalet de LlobregatHereditary Cancer Group, CARE Translational Program, Germans Trias i Pujol Research Institute (IGTP)Hereditary Cancer Group, CARE Translational Program, Germans Trias i Pujol Research Institute (IGTP)Hereditary Cancer Group, CARE Translational Program, Germans Trias i Pujol Research Institute (IGTP)Program in Molecular Mechanisms and Experimental Therapy in Oncology (Oncobell), IDIBELL, Hospitalet de LlobregatDepartment of Pediatric Surgery, Hospital Universitario La PazMedical Oncology, Hospital Universitario Insular de Gran CanariaHereditary Cancer Group, CARE Translational Program, Germans Trias i Pujol Research Institute (IGTP)Hereditary Cancer Program, Catalan Institute of Oncology (ICO-IDIBELL), Hospitalet de LlobregatHereditary Cancer Program, Catalan Institute of Oncology (ICO-IDIBELL), Hospitalet de LlobregatAbstract 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.https://doi.org/10.1186/s12935-025-03845-4Cellular modelMalignant peripheral nerve sheath tumorsNeurofibromatosis type 1NF1Sporadicand patient-derived xenograft |
| spellingShingle | Sara Ortega-Bertran Edgar Creus-Bachiller Miriam Magallón-Lorenz Meritxell Carrió Bernat Gel Alberto Villanueva Juan Carlos Lopez-Gutierrez Anna Estival Eduard Serra Juana Fernández-Rodríguez Conxi Lázaro New models for MPNST: establishment and comprehensive characterization of two tumor cell lines Cancer Cell International Cellular model Malignant peripheral nerve sheath tumors Neurofibromatosis type 1 NF1 Sporadic and patient-derived xenograft |
| title | 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_short | 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 |
| topic | Cellular model Malignant peripheral nerve sheath tumors Neurofibromatosis type 1 NF1 Sporadic and patient-derived xenograft |
| url | https://doi.org/10.1186/s12935-025-03845-4 |
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