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Tumor-Specific Chromosome Mis-Segregation Controls Cancer Plasticity by Maintaining Tumor Heterogeneity
Aneuploidy with chromosome instability is a cancer hallmark. We studied chromosome 7 (Chr7) copy number variation (CNV) in gliomas and in primary cultures derived from them. We found tumor heterogeneity with cells having Chr7-CNV commonly occurs in gliomas, with a higher percentage of cells in high-...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3839911/ https://www.ncbi.nlm.nih.gov/pubmed/24282558 http://dx.doi.org/10.1371/journal.pone.0080898 |
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author | Hu, Yuanjie Ru, Ning Xiao, Huasheng Chaturbedi, Abhishek Hoa, Neil T. Tian, Xiao-Jun Zhang, Hang Ke, Chao Yan, Fengrong Nelson, Jodi Li, Zhenzhi Gramer, Robert Yu, Liping Siegel, Eric Zhang, Xiaona Jia, Zhenyu Jadus, Martin R. Limoli, Charles L. Linskey, Mark E. Xing, Jianhua Zhou, Yi-Hong |
author_facet | Hu, Yuanjie Ru, Ning Xiao, Huasheng Chaturbedi, Abhishek Hoa, Neil T. Tian, Xiao-Jun Zhang, Hang Ke, Chao Yan, Fengrong Nelson, Jodi Li, Zhenzhi Gramer, Robert Yu, Liping Siegel, Eric Zhang, Xiaona Jia, Zhenyu Jadus, Martin R. Limoli, Charles L. Linskey, Mark E. Xing, Jianhua Zhou, Yi-Hong |
author_sort | Hu, Yuanjie |
collection | PubMed |
description | Aneuploidy with chromosome instability is a cancer hallmark. We studied chromosome 7 (Chr7) copy number variation (CNV) in gliomas and in primary cultures derived from them. We found tumor heterogeneity with cells having Chr7-CNV commonly occurs in gliomas, with a higher percentage of cells in high-grade gliomas carrying more than 2 copies of Chr7, as compared to low-grade gliomas. Interestingly, all Chr7-aneuploid cell types in the parental culture of established glioma cell lines reappeared in single-cell-derived subcultures. We then characterized the biology of three syngeneic glioma cultures dominated by different Chr7-aneuploid cell types. We found phenotypic divergence for cells following Chr7 mis-segregation, which benefited overall tumor growth in vitro and in vivo. Mathematical modeling suggested the involvement of chromosome instability and interactions among cell subpopulations in restoring the optimal equilibrium of tumor cell types. Both our experimental data and mathematical modeling demonstrated that the complexity of tumor heterogeneity could be enhanced by the existence of chromosomes with structural abnormality, in addition to their mis-segregations. Overall, our findings show, for the first time, the involvement of chromosome instability in maintaining tumor heterogeneity, which underlies the enhanced growth, persistence and treatment resistance of cancers. |
format | Online Article Text |
id | pubmed-3839911 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-38399112013-11-26 Tumor-Specific Chromosome Mis-Segregation Controls Cancer Plasticity by Maintaining Tumor Heterogeneity Hu, Yuanjie Ru, Ning Xiao, Huasheng Chaturbedi, Abhishek Hoa, Neil T. Tian, Xiao-Jun Zhang, Hang Ke, Chao Yan, Fengrong Nelson, Jodi Li, Zhenzhi Gramer, Robert Yu, Liping Siegel, Eric Zhang, Xiaona Jia, Zhenyu Jadus, Martin R. Limoli, Charles L. Linskey, Mark E. Xing, Jianhua Zhou, Yi-Hong PLoS One Research Article Aneuploidy with chromosome instability is a cancer hallmark. We studied chromosome 7 (Chr7) copy number variation (CNV) in gliomas and in primary cultures derived from them. We found tumor heterogeneity with cells having Chr7-CNV commonly occurs in gliomas, with a higher percentage of cells in high-grade gliomas carrying more than 2 copies of Chr7, as compared to low-grade gliomas. Interestingly, all Chr7-aneuploid cell types in the parental culture of established glioma cell lines reappeared in single-cell-derived subcultures. We then characterized the biology of three syngeneic glioma cultures dominated by different Chr7-aneuploid cell types. We found phenotypic divergence for cells following Chr7 mis-segregation, which benefited overall tumor growth in vitro and in vivo. Mathematical modeling suggested the involvement of chromosome instability and interactions among cell subpopulations in restoring the optimal equilibrium of tumor cell types. Both our experimental data and mathematical modeling demonstrated that the complexity of tumor heterogeneity could be enhanced by the existence of chromosomes with structural abnormality, in addition to their mis-segregations. Overall, our findings show, for the first time, the involvement of chromosome instability in maintaining tumor heterogeneity, which underlies the enhanced growth, persistence and treatment resistance of cancers. Public Library of Science 2013-11-25 /pmc/articles/PMC3839911/ /pubmed/24282558 http://dx.doi.org/10.1371/journal.pone.0080898 Text en © 2013 Hu et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Hu, Yuanjie Ru, Ning Xiao, Huasheng Chaturbedi, Abhishek Hoa, Neil T. Tian, Xiao-Jun Zhang, Hang Ke, Chao Yan, Fengrong Nelson, Jodi Li, Zhenzhi Gramer, Robert Yu, Liping Siegel, Eric Zhang, Xiaona Jia, Zhenyu Jadus, Martin R. Limoli, Charles L. Linskey, Mark E. Xing, Jianhua Zhou, Yi-Hong Tumor-Specific Chromosome Mis-Segregation Controls Cancer Plasticity by Maintaining Tumor Heterogeneity |
title | Tumor-Specific Chromosome Mis-Segregation Controls Cancer Plasticity by Maintaining Tumor Heterogeneity |
title_full | Tumor-Specific Chromosome Mis-Segregation Controls Cancer Plasticity by Maintaining Tumor Heterogeneity |
title_fullStr | Tumor-Specific Chromosome Mis-Segregation Controls Cancer Plasticity by Maintaining Tumor Heterogeneity |
title_full_unstemmed | Tumor-Specific Chromosome Mis-Segregation Controls Cancer Plasticity by Maintaining Tumor Heterogeneity |
title_short | Tumor-Specific Chromosome Mis-Segregation Controls Cancer Plasticity by Maintaining Tumor Heterogeneity |
title_sort | tumor-specific chromosome mis-segregation controls cancer plasticity by maintaining tumor heterogeneity |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3839911/ https://www.ncbi.nlm.nih.gov/pubmed/24282558 http://dx.doi.org/10.1371/journal.pone.0080898 |
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