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Microenvironment-Dependent Phenotypic Changes in a SCID Mouse Model for Malignant Mesothelioma
Background and Aims: Malignant mesothelioma is an aggressive, therapy-resistant tumor. Mesothelioma cells may assume an epithelioid or a sarcomatoid phenotype, and presence of sarcomatoid cells predicts poor prognosis. In this study, we investigated differentiation of mesothelioma cells in a xenogra...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3739415/ https://www.ncbi.nlm.nih.gov/pubmed/23951555 http://dx.doi.org/10.3389/fonc.2013.00203 |
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author | Darai-Ramqvist, Eva Nilsonne, Gustav Flores-Staino, Carmen Hjerpe, Anders Dobra, Katalin |
author_facet | Darai-Ramqvist, Eva Nilsonne, Gustav Flores-Staino, Carmen Hjerpe, Anders Dobra, Katalin |
author_sort | Darai-Ramqvist, Eva |
collection | PubMed |
description | Background and Aims: Malignant mesothelioma is an aggressive, therapy-resistant tumor. Mesothelioma cells may assume an epithelioid or a sarcomatoid phenotype, and presence of sarcomatoid cells predicts poor prognosis. In this study, we investigated differentiation of mesothelioma cells in a xenograft model, where mesothelioma cells of both phenotypes were induced to form tumors in severe combined immunodeficiency mice. Methods: Xenografts were established and thoroughly characterized using a comprehensive immunohistochemical panel, array comparative genomic hybridization (aCGH) of chromosome 3, fluorescent in situ hybridization, and electron microscopy. Results: Epithelioid and sarcomatoid cells gave rise to xenografts of similar epithelioid morphology. While sarcomatoid-derived xenografts had higher growth rates, the morphology and expression of differentiation-related markers was similar between xenografts derived from both phenotypes. aCGH showed a convergent genotype for both xenografts, resembling the original aggressive sarcomatoid cell sub-line. Conclusion: Human mesothelioma xenografts from sarcomatoid and epithelioid phenotypes converged to a similar differentiation state, and genetic analyses suggested that clonal selection in the mouse microenvironment was a major contributing factor. This thoroughly characterized animal model can be used for further studies of molecular events underlying tumor cell differentiation. |
format | Online Article Text |
id | pubmed-3739415 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-37394152013-08-15 Microenvironment-Dependent Phenotypic Changes in a SCID Mouse Model for Malignant Mesothelioma Darai-Ramqvist, Eva Nilsonne, Gustav Flores-Staino, Carmen Hjerpe, Anders Dobra, Katalin Front Oncol Oncology Background and Aims: Malignant mesothelioma is an aggressive, therapy-resistant tumor. Mesothelioma cells may assume an epithelioid or a sarcomatoid phenotype, and presence of sarcomatoid cells predicts poor prognosis. In this study, we investigated differentiation of mesothelioma cells in a xenograft model, where mesothelioma cells of both phenotypes were induced to form tumors in severe combined immunodeficiency mice. Methods: Xenografts were established and thoroughly characterized using a comprehensive immunohistochemical panel, array comparative genomic hybridization (aCGH) of chromosome 3, fluorescent in situ hybridization, and electron microscopy. Results: Epithelioid and sarcomatoid cells gave rise to xenografts of similar epithelioid morphology. While sarcomatoid-derived xenografts had higher growth rates, the morphology and expression of differentiation-related markers was similar between xenografts derived from both phenotypes. aCGH showed a convergent genotype for both xenografts, resembling the original aggressive sarcomatoid cell sub-line. Conclusion: Human mesothelioma xenografts from sarcomatoid and epithelioid phenotypes converged to a similar differentiation state, and genetic analyses suggested that clonal selection in the mouse microenvironment was a major contributing factor. This thoroughly characterized animal model can be used for further studies of molecular events underlying tumor cell differentiation. Frontiers Media S.A. 2013-08-09 /pmc/articles/PMC3739415/ /pubmed/23951555 http://dx.doi.org/10.3389/fonc.2013.00203 Text en Copyright © 2013 Darai-Ramqvist, Nilsonne, Flores-Staino, Hjerpe and Dobra. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Darai-Ramqvist, Eva Nilsonne, Gustav Flores-Staino, Carmen Hjerpe, Anders Dobra, Katalin Microenvironment-Dependent Phenotypic Changes in a SCID Mouse Model for Malignant Mesothelioma |
title | Microenvironment-Dependent Phenotypic Changes in a SCID Mouse Model for Malignant Mesothelioma |
title_full | Microenvironment-Dependent Phenotypic Changes in a SCID Mouse Model for Malignant Mesothelioma |
title_fullStr | Microenvironment-Dependent Phenotypic Changes in a SCID Mouse Model for Malignant Mesothelioma |
title_full_unstemmed | Microenvironment-Dependent Phenotypic Changes in a SCID Mouse Model for Malignant Mesothelioma |
title_short | Microenvironment-Dependent Phenotypic Changes in a SCID Mouse Model for Malignant Mesothelioma |
title_sort | microenvironment-dependent phenotypic changes in a scid mouse model for malignant mesothelioma |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3739415/ https://www.ncbi.nlm.nih.gov/pubmed/23951555 http://dx.doi.org/10.3389/fonc.2013.00203 |
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