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

J 2020

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

ŠKODA, Jan, Jakub NERADIL, Iva STANICZKOVÁ ZAMBO, Alena ŇUŇUKOVÁ, Peter MACSEK et. al.

Basic information

Original name

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

Authors

ŠKODA, Jan (203 Czech Republic, belonging to the institution), Jakub NERADIL (203 Czech Republic, guarantor, belonging to the institution), Iva STANICZKOVÁ ZAMBO (203 Czech Republic, belonging to the institution), Alena ŇUŇUKOVÁ (703 Slovakia, belonging to the institution), Peter MACSEK (703 Slovakia, belonging to the institution), Karolína BOŘÁNKOVÁ (203 Czech Republic, belonging to the institution), Viera DOBROTKOVÁ (703 Slovakia, belonging to the institution), Pavel NĚMEC (203 Czech Republic, belonging to the institution), Jaroslav ŠTĚRBA (203 Czech Republic, belonging to the institution) and Renata VESELSKÁ (203 Czech Republic, belonging to the institution)

Edition

Cancers, BASEL, MDPI, 2020, 2072-6694

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 6.639

RIV identification code

RIV/00216224:14310/20:00116903

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.3390/cancers12010196

UT WoS

000516826700196

Keywords in English

rhabdomyosarcoma; cancer stem cells; stemness; stem-like state; serial xenotransplantation; in vivo tumorigenicity assay; epithelial; mesenchymal phenotype

Abstract

V originále

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.

Links

MUNI/A/1409/2019, interní kód MU

Name: Personalizovaná léčba v dětské onkologii: na cestě k "liquid dynamic medicine" a "N-of-1 clinical trials"

Investor: Masaryk University, Category A

NT13443, research and development project

Name: Identifikace a charakterizace nádorových kmenových buněk u sarkomů dětského věku.

Citovat

ŠKODA, Jan, Jakub NERADIL, Iva STANICZKOVÁ ZAMBO, Alena ŇUŇUKOVÁ, Peter MACSEK, Karolína BOŘÁNKOVÁ, Viera DOBROTKOVÁ, Pavel NĚMEC, Jaroslav ŠTĚRBA and Renata VESELSKÁ. Serial Xenotransplantation in NSG Mice Promotes a Hybrid Epithelial/Mesenchymal Gene Expression Signature and Stemness in Rhabdomyosarcoma Cells. Cancers. BASEL: MDPI, 2020, vol. 12, No 1, p. 1-24. ISSN 2072-6694. Available from: https://dx.doi.org/10.3390/cancers12010196.

@article{1691996,
   author = {Škoda, Jan and Neradil, Jakub and Staniczková Zambo, Iva and Ňuňuková, Alena and Macsek, Peter and Bořánková, Karolína and Dobrotková, Viera and Němec, Pavel and Štěrba, Jaroslav and Veselská, Renata},
   article_location = {BASEL},
   article_number = {1},
   doi = {http://dx.doi.org/10.3390/cancers12010196},
   keywords = {rhabdomyosarcoma; cancer stem cells; stemness; stem-like state; serial xenotransplantation; in vivo tumorigenicity assay; epithelial; mesenchymal phenotype},
   language = {eng},
   issn = {2072-6694},
   journal = {Cancers},
   title = {Serial Xenotransplantation in NSG Mice Promotes a Hybrid Epithelial/Mesenchymal Gene Expression Signature and Stemness in Rhabdomyosarcoma Cells},
   url = {https://www.mdpi.com/2072-6694/12/1/196},
   volume = {12},
   year = {2020}
}

TY  - JOUR
ID  - 1691996
AU  - Škoda, Jan - Neradil, Jakub - Staniczková Zambo, Iva - Ňuňuková, Alena - Macsek, Peter - Bořánková, Karolína - Dobrotková, Viera - Němec, Pavel - Štěrba, Jaroslav - Veselská, Renata
PY  - 2020
TI  - Serial Xenotransplantation in NSG Mice Promotes a Hybrid Epithelial/Mesenchymal Gene Expression Signature and Stemness in Rhabdomyosarcoma Cells
JF  - Cancers
VL  - 12
IS  - 1
SP  - 1-24
EP  - 1-24
PB  - MDPI
SN  - 20726694
KW  - rhabdomyosarcoma
KW  - cancer stem cells
KW  - stemness
KW  - stem-like state
KW  - serial xenotransplantation
KW  - in vivo tumorigenicity assay
KW  - epithelial
KW  - mesenchymal phenotype
UR  - https://www.mdpi.com/2072-6694/12/1/196
L2  - https://www.mdpi.com/2072-6694/12/1/196
N2  - 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.
ER  -

ŠKODA, Jan, Jakub NERADIL, Iva STANICZKOVÁ ZAMBO, Alena ŇUŇUKOVÁ, Peter MACSEK, Karolína BOŘÁNKOVÁ, Viera DOBROTKOVÁ, Pavel NĚMEC, Jaroslav ŠTĚRBA and Renata VESELSKÁ. Serial Xenotransplantation in NSG Mice Promotes a Hybrid Epithelial/Mesenchymal Gene Expression Signature and Stemness in Rhabdomyosarcoma Cells. \textit{Cancers}. BASEL: MDPI, 2020, vol.~12, No~1, p.~1-24. ISSN~2072-6694. Available from: https://dx.doi.org/10.3390/cancers12010196.

Detailed Information on Publication Record