Putative cancer stem cells may be the key target to inhibit cancer cell repopulation between the intervals of chemoradiation in murine mesothelioma
Abstract Background 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 eventua...
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doaj-0356c2c246ab4de6bc26892cd21626322020-11-25T00:32:12ZengBMCBMC Cancer1471-24072018-04-0118111410.1186/s12885-018-4354-1Putative cancer stem cells may be the key target to inhibit cancer cell repopulation between the intervals of chemoradiation in murine mesotheliomaLicun Wu0Walter Blum1Chang-Qi Zhu2Zhihong Yun3Laszlo Pecze4Mikihiro Kohno5Mei-Lin Chan6Yidan Zhao7Emanuela Felley-Bosco8Beat Schwaller9Marc de Perrot10Division of Thoracic Surgery, Latner Thoracic Surgery LaboratoriesDepartment of Medicine, Unit of Anatomy, University of FribourgPrincess Margaret Cancer Centre, University Health NetworkDivision of Thoracic Surgery, Latner Thoracic Surgery LaboratoriesDepartment of Medicine, Unit of Anatomy, University of FribourgDivision of Thoracic Surgery, Latner Thoracic Surgery LaboratoriesDivision of Thoracic Surgery, Latner Thoracic Surgery LaboratoriesDivision of Thoracic Surgery, Latner Thoracic Surgery LaboratoriesLaboratory of Molecular Oncology, University Hospital Zurich, University of ZurichDepartment of Medicine, Unit of Anatomy, University of FribourgDivision of Thoracic Surgery, Latner Thoracic Surgery LaboratoriesAbstract Background 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. Methods 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. Results 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. Conclusion 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.http://link.springer.com/article/10.1186/s12885-018-4354-1Mesothelioma stem cell (MSC)RN5-EOS-Puro2 cellsCancer cell repopulationMicroarrayChemoradiation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Licun Wu Walter Blum Chang-Qi Zhu Zhihong Yun Laszlo Pecze Mikihiro Kohno Mei-Lin Chan Yidan Zhao Emanuela Felley-Bosco Beat Schwaller Marc de Perrot |
spellingShingle |
Licun Wu Walter Blum Chang-Qi Zhu Zhihong Yun Laszlo Pecze Mikihiro Kohno Mei-Lin Chan Yidan Zhao Emanuela Felley-Bosco Beat Schwaller Marc de Perrot Putative cancer stem cells may be the key target to inhibit cancer cell repopulation between the intervals of chemoradiation in murine mesothelioma BMC Cancer Mesothelioma stem cell (MSC) RN5-EOS-Puro2 cells Cancer cell repopulation Microarray Chemoradiation |
author_facet |
Licun Wu Walter Blum Chang-Qi Zhu Zhihong Yun Laszlo Pecze Mikihiro Kohno Mei-Lin Chan Yidan Zhao Emanuela Felley-Bosco Beat Schwaller Marc de Perrot |
author_sort |
Licun Wu |
title |
Putative cancer stem cells may be the key target to inhibit cancer cell repopulation between the intervals of chemoradiation in murine mesothelioma |
title_short |
Putative cancer stem cells may be the key target to inhibit cancer cell repopulation between the intervals of chemoradiation in murine mesothelioma |
title_full |
Putative cancer stem cells may be the key target to inhibit cancer cell repopulation between the intervals of chemoradiation in murine mesothelioma |
title_fullStr |
Putative cancer stem cells may be the key target to inhibit cancer cell repopulation between the intervals of chemoradiation in murine mesothelioma |
title_full_unstemmed |
Putative cancer stem cells may be the key target to inhibit cancer cell repopulation between the intervals of chemoradiation in murine mesothelioma |
title_sort |
putative cancer stem cells may be the key target to inhibit cancer cell repopulation between the intervals of chemoradiation in murine mesothelioma |
publisher |
BMC |
series |
BMC Cancer |
issn |
1471-2407 |
publishDate |
2018-04-01 |
description |
Abstract Background 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. Methods 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. Results 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. Conclusion 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. |
topic |
Mesothelioma stem cell (MSC) RN5-EOS-Puro2 cells Cancer cell repopulation Microarray Chemoradiation |
url |
http://link.springer.com/article/10.1186/s12885-018-4354-1 |
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