Serial Xenotransplantation in NSG Mice Promotes a Hybrid Epithelial/Mesenchymal Gene Expression Signature and Stemness in Rhabdomyosarcoma Cells

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F20%3A00072733" target="_blank" >RIV/00159816:_____/20:00072733 - isvavai.cz</a>

Alternative codes found

RIV/00216224:14310/20:00116903 RIV/65269705:_____/20:00072733

Result on the web

<a href="https://www.mdpi.com/2072-6694/12/1/196" target="_blank" >https://www.mdpi.com/2072-6694/12/1/196</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/cancers12010196" target="_blank" >10.3390/cancers12010196</a>

Result language

angličtina

Original language name

Serial Xenotransplantation in NSG Mice Promotes a Hybrid Epithelial/Mesenchymal Gene Expression Signature and Stemness in Rhabdomyosarcoma Cells

Original language description

Serial xenotransplantation of sorted cancer cells in immunodeficient mice remains the most complex test of cancer stem cell (CSC) phenotype. However, we have demonstrated in various sarcomas that putative CSC surface markers fail to identify CSCs, thereby impeding the isolation of CSCs for subsequent analyses. Here, we utilized serial xenotransplantation of unsorted rhabdomyosarcoma cells in NOD/SCID gamma (NSG) mice as a proof-of-principle platform to investigate the molecular signature of CSCs. Indeed, serial xenotransplantation steadily enriched for rhabdomyosarcoma stem-like cells characterized by enhanced aldehyde dehydrogenase activity and increased colony and sphere formation capacity in vitro. Although the expression of core pluripotency factors (SOX2, OCT4, NANOG) and common CSC markers (CD133, ABCG2, nestin) was maintained over the passages in mice, gene expression profiling revealed gradual changes in several stemness regulators and genes linked with undifferentiated myogenic precursors, e.g., SOX4, PAX3, MIR145, and CDH15. Moreover, we identified the induction of a hybrid epithelial/mesenchymal gene expression signature that was associated with the increase in CSC number. In total, 60 genes related to epithelial or mesenchymal traits were significantly altered upon serial xenotransplantation. In silico survival analysis based on the identified potential stemness-associated genes demonstrated that serial xenotransplantation of unsorted rhabdomyosarcoma cells in NSG mice might be a useful tool for the unbiased enrichment of CSCs and the identification of novel CSC-specific targets. Using this approach, we provide evidence for a recently proposed link between the hybrid epithelial/mesenchymal phenotype and cancer stemness.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30204 - Oncology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2020

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Cancers

ISSN

2072-6694

e-ISSN

—

Volume of the periodical

12

Issue of the periodical within the volume

1

Country of publishing house

CH - SWITZERLAND

Number of pages

24

Pages from-to

196

UT code for WoS article

000516826700196

EID of the result in the Scopus database

2-s2.0-85078269878