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Loss of Nf1 and Ink4a/Arf Are Associated with Sex-Dependent Growth Differences in a Mouse Model of Embryonal Rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is an aggressive form of cancer that accounts for half of all pediatric soft tissue sarcomas. Little progress has been made in improving survival outcomes over the past three decades. Mouse models of rhabdomyosarcoma are a critical component of translational research aimed at...

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Autores principales: Gutierrez, Wade R., Rytlewski, Jeffrey D., Scherer, Amanda, Roughton, Grace A., Carnevale, Nina C., Vyas, Krisha Y., McGivney, Gavin R., Brockman, Qierra R., Knepper-Adrian, Vickie, Dodd, Rebecca D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9955904/
https://www.ncbi.nlm.nih.gov/pubmed/36826025
http://dx.doi.org/10.3390/cimb45020080
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author Gutierrez, Wade R.
Rytlewski, Jeffrey D.
Scherer, Amanda
Roughton, Grace A.
Carnevale, Nina C.
Vyas, Krisha Y.
McGivney, Gavin R.
Brockman, Qierra R.
Knepper-Adrian, Vickie
Dodd, Rebecca D.
author_facet Gutierrez, Wade R.
Rytlewski, Jeffrey D.
Scherer, Amanda
Roughton, Grace A.
Carnevale, Nina C.
Vyas, Krisha Y.
McGivney, Gavin R.
Brockman, Qierra R.
Knepper-Adrian, Vickie
Dodd, Rebecca D.
author_sort Gutierrez, Wade R.
collection PubMed
description Rhabdomyosarcoma (RMS) is an aggressive form of cancer that accounts for half of all pediatric soft tissue sarcomas. Little progress has been made in improving survival outcomes over the past three decades. Mouse models of rhabdomyosarcoma are a critical component of translational research aimed at understanding tumor biology and developing new, improved therapies. Though several models exist, many common mutations found in human rhabdomyosarcoma tumors remain unmodeled and understudied. This study describes a new model of embryonal rhabdomyosarcoma driven by the loss of Nf1 and Ink4a/Arf, two mutations commonly found in patient tumors. We find that this new model is histologically similar to other previously-published rhabdomyosarcoma models, although it substantially differs in the time required for tumor onset and in tumor growth kinetics. We also observe unique sex-dependent phenotypes in both primary and newly-developed orthotopic syngeneic allograft tumors that are not present in previous models. Using in vitro and in vivo studies, we examined the response to vincristine, a component of the standard-of-care chemotherapy for RMS. The findings from this study provide valuable insight into a new mouse model of rhabdomyosarcoma that addresses an ongoing need for patient-relevant animal models to further translational research.
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spelling pubmed-99559042023-02-25 Loss of Nf1 and Ink4a/Arf Are Associated with Sex-Dependent Growth Differences in a Mouse Model of Embryonal Rhabdomyosarcoma Gutierrez, Wade R. Rytlewski, Jeffrey D. Scherer, Amanda Roughton, Grace A. Carnevale, Nina C. Vyas, Krisha Y. McGivney, Gavin R. Brockman, Qierra R. Knepper-Adrian, Vickie Dodd, Rebecca D. Curr Issues Mol Biol Article Rhabdomyosarcoma (RMS) is an aggressive form of cancer that accounts for half of all pediatric soft tissue sarcomas. Little progress has been made in improving survival outcomes over the past three decades. Mouse models of rhabdomyosarcoma are a critical component of translational research aimed at understanding tumor biology and developing new, improved therapies. Though several models exist, many common mutations found in human rhabdomyosarcoma tumors remain unmodeled and understudied. This study describes a new model of embryonal rhabdomyosarcoma driven by the loss of Nf1 and Ink4a/Arf, two mutations commonly found in patient tumors. We find that this new model is histologically similar to other previously-published rhabdomyosarcoma models, although it substantially differs in the time required for tumor onset and in tumor growth kinetics. We also observe unique sex-dependent phenotypes in both primary and newly-developed orthotopic syngeneic allograft tumors that are not present in previous models. Using in vitro and in vivo studies, we examined the response to vincristine, a component of the standard-of-care chemotherapy for RMS. The findings from this study provide valuable insight into a new mouse model of rhabdomyosarcoma that addresses an ongoing need for patient-relevant animal models to further translational research. MDPI 2023-02-02 /pmc/articles/PMC9955904/ /pubmed/36826025 http://dx.doi.org/10.3390/cimb45020080 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gutierrez, Wade R.
Rytlewski, Jeffrey D.
Scherer, Amanda
Roughton, Grace A.
Carnevale, Nina C.
Vyas, Krisha Y.
McGivney, Gavin R.
Brockman, Qierra R.
Knepper-Adrian, Vickie
Dodd, Rebecca D.
Loss of Nf1 and Ink4a/Arf Are Associated with Sex-Dependent Growth Differences in a Mouse Model of Embryonal Rhabdomyosarcoma
title Loss of Nf1 and Ink4a/Arf Are Associated with Sex-Dependent Growth Differences in a Mouse Model of Embryonal Rhabdomyosarcoma
title_full Loss of Nf1 and Ink4a/Arf Are Associated with Sex-Dependent Growth Differences in a Mouse Model of Embryonal Rhabdomyosarcoma
title_fullStr Loss of Nf1 and Ink4a/Arf Are Associated with Sex-Dependent Growth Differences in a Mouse Model of Embryonal Rhabdomyosarcoma
title_full_unstemmed Loss of Nf1 and Ink4a/Arf Are Associated with Sex-Dependent Growth Differences in a Mouse Model of Embryonal Rhabdomyosarcoma
title_short Loss of Nf1 and Ink4a/Arf Are Associated with Sex-Dependent Growth Differences in a Mouse Model of Embryonal Rhabdomyosarcoma
title_sort loss of nf1 and ink4a/arf are associated with sex-dependent growth differences in a mouse model of embryonal rhabdomyosarcoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9955904/
https://www.ncbi.nlm.nih.gov/pubmed/36826025
http://dx.doi.org/10.3390/cimb45020080
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