Modeling Ewing Sarcoma Lung Metastasis

Authors

Atreyi Dasgupta
Lyazat Kurenbekova
Tajhal D Patel
Kimal Rajapakshe
Gargi Ghosal
Bikesh Nirala
Cristian Coarfa
Jason Yustein

Publication Date

2-1-2023

Journal

Current Protocols

DOI

10.1002/cpz1.670

PMID

36799651

PMCID

PMC9942121

PubMedCentral® Posted Date

2-1-2024

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

Keywords

Animals, Mice, Sarcoma, Ewing, RNA-Binding Protein EWS, Bone Neoplasms, Neuroectodermal Tumors, Primitive, Peripheral, Lung Neoplasms

Abstract

Ewing Sarcoma (EwS) is the second most common malignant bone tumor in adolescents and young adults. The single-most powerful predictor of outcome in EwS is presence of metastatic burden at the time of diagnosis. Patients with metastatic Ewing Sarcoma have an abysmal 5-year survival rate of 10–25%, which has not changed over the past 30–40 years. Thus, unraveling underlying mechanisms of EwS metastasis are imperative for developing effective therapeutic measures. Investigations towards this goal are limited by the lack of reliable genetically engineered mouse models and specialized metastatic models. Using two established cell lines, A673 and TC71, we generated lung specific metastatic cell lines by serial orthotopic intra-tibial injection followed by isolation of cells from lung metastases. The lung metastatic lines generated exhibit distinct differential molecular signatures from the parental cells when analyzed using a multi-omics approach. These signatures overlapped with EwS patient primary bone and metastatic lung specimens supporting the clinical relevance of these preclinical models of EwS.

Basic Protocol 1: (Intratibial Injection in Immunocompromised Mice)

Basic Protocol 2: (Development and Characterization of Lung Metastatic Cell Line)

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