Experimental Models of Undifferentiated Pleomorphic Sarcoma and Malignant Peripheral Nerve Sheath Tumor

Authors

Angela D Bhalla
Sharon M Landers
Anand K Singh
Jace P Landry
Michelle G Yeagley
Gabryella S B Myerson
Cristian B Delgado-Baez
Stephanie Dunnand
Theresa Nguyen
Xiaoyan Ma
Svetlana Bolshakov
Brian A Menegaz
Salah-Eddine Lamhamedi-Cherradi
Xizeng Mao
Xingzhi Song
Alexander J Lazar
Ian E McCutcheon
John M Slopis
Joseph A Ludwig
Dina C Lev
Kunal Rai
Keila E Torres

Publication Date

6-1-2022

Journal

Laboratory Investigation

Abstract

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.

Keywords

Animals, Humans, Mice, Models, Theoretical, Mutation, Neurofibrosarcoma, Sarcoma, Soft Tissue Neoplasms

DOI

10.1038/s41374-022-00734-6

PMID

35228656

PMCID

PMC11959861

PubMedCentral® Posted Date

4-1-2025

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes