A multimodal treatment of carbon ions irradiation, miRNA-34 and mTOR inhibitor specifically control high-grade chondrosarcoma cancer stem cells.
Cancer stem cell
Chondrosarcoma
Particle therapy
mTOR inhibitor
miR-34
Journal
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
ISSN: 1879-0887
Titre abrégé: Radiother Oncol
Pays: Ireland
ID NLM: 8407192
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
29
01
2020
revised:
20
07
2020
accepted:
20
07
2020
pubmed:
28
7
2020
medline:
15
4
2021
entrez:
28
7
2020
Statut:
ppublish
Résumé
High-grade chondrosarcomas are chemo- and radio-resistant cartilage-forming tumors of bone that often relapse and metastase. Thus, new therapeutic strategies are urgently needed. Chondrosarcoma cells (CH-2879) were exposed to carbon-ion irradiation, combined with miR-34 mimic and/or rapamycin administration. The effects of treatment on cancer stem cells, stemness-associated phenotype, radioresistance and tumor-initiating properties were evaluated. We show that high-grade chondrosarcoma cells contain a population of radioresistant cancer stem cells that can be targeted by a combination of carbon-ion therapy, miR-34 mimic administration and/or rapamycin treatment that triggers FOXO3 and miR-34 over-expression. mTOR inhibition by rapamycin triggered FOXO3 and miR-34, leading to KLF4 repression. Our results show that particle therapy combined with molecular treatments effectively controls cancer stem cells and may overcome treatment resistance of high-grade chondrosarcoma.
Sections du résumé
BACKGROUND AND PURPOSE
High-grade chondrosarcomas are chemo- and radio-resistant cartilage-forming tumors of bone that often relapse and metastase. Thus, new therapeutic strategies are urgently needed.
MATERIAL AND METHODS
Chondrosarcoma cells (CH-2879) were exposed to carbon-ion irradiation, combined with miR-34 mimic and/or rapamycin administration. The effects of treatment on cancer stem cells, stemness-associated phenotype, radioresistance and tumor-initiating properties were evaluated.
RESULTS
We show that high-grade chondrosarcoma cells contain a population of radioresistant cancer stem cells that can be targeted by a combination of carbon-ion therapy, miR-34 mimic administration and/or rapamycin treatment that triggers FOXO3 and miR-34 over-expression. mTOR inhibition by rapamycin triggered FOXO3 and miR-34, leading to KLF4 repression.
CONCLUSION
Our results show that particle therapy combined with molecular treatments effectively controls cancer stem cells and may overcome treatment resistance of high-grade chondrosarcoma.
Identifiants
pubmed: 32717360
pii: S0167-8140(20)30679-4
doi: 10.1016/j.radonc.2020.07.034
pii:
doi:
Substances chimiques
Ions
0
KLF4 protein, human
0
Kruppel-Like Factor 4
0
MIRN34 microRNA, human
0
MicroRNAs
0
Carbon
7440-44-0
MTOR protein, human
EC 2.7.1.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
253-261Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.