Experimental models of undifferentiated pleomorphic sarcoma and malignant peripheral nerve sheath tumor.
Journal
Laboratory investigation; a journal of technical methods and pathology
ISSN: 1530-0307
Titre abrégé: Lab Invest
Pays: United States
ID NLM: 0376617
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
received:
05
11
2021
accepted:
06
01
2022
revised:
29
12
2021
pubmed:
2
3
2022
medline:
7
6
2022
entrez:
1
3
2022
Statut:
ppublish
Résumé
Undifferentiated pleomorphic sarcoma (UPS) and malignant peripheral nerve sheath tumor (MPNST) are aggressive soft tissue sarcomas that do not respond well to current treatment modalities. The limited availability of UPS and MPNST cell lines makes it challenging to identify potential therapeutic targets in a laboratory setting. Understanding the urgent need for improved treatments for these tumors and the limited cellular models available, we generated additional cell lines to study these rare cancers. Patient-derived tumors were used to establish 4 new UPS models, including one radiation-associated UPS-UPS271.1, UPS511, UPS0103, and RIS620, one unclassified spindle cell sarcoma-USC060.1, and 3 new models of MPNST-MPNST007, MPNST3813E, and MPNST4970. This study examined the utility of the new cell lines as sarcoma models by assessing their tumorigenic potential and mutation status for known sarcoma-related genes. All the cell lines formed colonies and migrated in vitro. The in vivo tumorigenic potential of the cell lines and corresponding xenografts was determined by subcutaneous injection or xenograft re-passaging into immunocompromised mice. USC060.1 and UPS511 cells formed tumors in mice upon subcutaneous injection. UPS0103 and RIS620 tumor implants formed tumors in vivo, as did MPNST007 and MPNST3813E tumor implants. Targeted sequencing analysis of a panel of genes frequently mutated in sarcomas identified TP53, RB1, and ATRX mutations in a subset of the cell lines. These new cellular models provide the scientific community with powerful tools for detailed studies of tumorigenesis and for investigating novel therapies for UPS and MPNST.
Identifiants
pubmed: 35228656
doi: 10.1038/s41374-022-00734-6
pii: S0023-6837(22)00031-9
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
658-666Subventions
Organisme : NCI NIH HHS
ID : T32 CA009599
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA096300
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA096297
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Informations de copyright
© 2022. The Author(s), under exclusive licence to United States and Canadian Academy of Pathology.
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