Putative cancer stem cells may be the key target to inhibit cancer cell repopulation between the intervals of chemoradiation in murine mesothelioma.

Details

Serval ID
serval:BIB_649E15140F90
Type
Article: article from journal or magazin.
Collection
Publications
Title
Putative cancer stem cells may be the key target to inhibit cancer cell repopulation between the intervals of chemoradiation in murine mesothelioma.
Journal
BMC cancer
Author(s)
Wu L., Blum W., Zhu C.Q., Yun Z., Pecze L., Kohno M., Chan M.L., Zhao Y., Felley-Bosco E., Schwaller B., de Perrot M.
ISSN
1471-2407 (Electronic)
ISSN-L
1471-2407
Publication state
Published
Issued date
27/04/2018
Peer-reviewed
Oui
Volume
18
Number
1
Pages
471
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Cancer cell repopulation during chemotherapy or radiotherapy is a major factor limiting the efficacy of treatment. Cancer stem cells (CSC) may play critical roles during this process. We aim to demonstrate the role of mesothelioma stem cells (MSC) in treatment failure and eventually to design specific target therapies against MSC to improve the efficacy of treatment in malignant mesothelioma.
Murine mesothelioma AB12 and RN5 cells were used to compare tumorigenicity in mice. The expression of CSC-associated genes was evaluated by quantitative real-time PCR in both cell lines treated with chemo-radiation. Stemness properties of MSC-enriched RN5-EOS-Puro2 cells were characterized with flow cytometry and immunostaining. A MSC-specific gene profile was screened by microarray assay and confirmed thereafter. Gene Ontology analysis of the selected genes was performed by GOMiner.
Tumor growth delay of murine mesothelioma AB12 cells was achieved after each cycle of cisplatin treatment, however, tumors grew back rapidly due to cancer cell repopulation between courses of chemotherapy. Strikingly, a 10-times lower number of irradiated cells in both cell lines led to a similar tumor incidence and growth rate as with untreated cells. The expression of CSC-associated genes such as CD24, CD133, CD90 and uPAR was dramatically up-regulated, while others did not change significantly after chemoradiation. Highly enriched MSC after selection with puromycin displayed an increasing GFP-positive population and showed typical properties of stemness. Comparatively, the proportion of MSC significantly increased after RN5-EOS parental cells were treated with either chemotherapy, γ-ray radiation, or a combination of the two, while MSC showed more resistance to the above treatments. A group of identified genes are most likely MSC-specific, and major pathways related to regulation of cell growth or apoptosis are involved. Upregulation of the gene transcripts Tnfsf18, Serpinb9b, Ly6a, and Nppb were confirmed.
Putative MSC possess the property of stemness showing more resistance to chemoradiation, suggesting that MSC may play critical roles in cancer cell repopulation. Further identification of selected genes may be used to design novel target therapies against MSC, so as to eliminate cancer cell repopulation in mesothelioma.
Keywords
Cancer cell repopulation, Chemoradiation, Mesothelioma stem cell (MSC), Microarray, RN5-EOS-Puro2 cells
Pubmed
Web of science
Open Access
Yes
Create date
20/08/2018 14:52
Last modification date
20/08/2019 14:20
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