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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Bibliographic Details
Published in:	Current issues in molecular biology Vol. 45; no. 2; pp. 1218 - 1232
Main Authors:	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
Format:	Journal Article
Language:	English
Published:	Switzerland MDPI 01-02-2023 MDPI AG
Subjects:	cancer Ink4a/Arf mouse model Nf1 rhabdomyosarcoma sarcoma Ink4a/Arf sarcoma vincristine mouse model Nf1 cancer rhabdomyosarcoma
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1467-3045 1467-3037 1467-3045
DOI:	10.3390/cimb45020080