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Tumour formation by single fibroblast growth factor receptor 3-positive rhabdomyosarcoma-initiating cells
BACKGROUND: The hypothesis that malignant tumours are generated by rare populations of cancer stem cells that are more tumourigenic than other cancer cells has gained increasing credence. The objective of this study was to identify and characterise a subpopulation of human sarcoma-initiating cells....
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2795447/ https://www.ncbi.nlm.nih.gov/pubmed/19888223 http://dx.doi.org/10.1038/sj.bjc.6605407 |
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author | Hirotsu, M Setoguchi, T Matsunoshita, Y Sasaki, H Nagao, H Gao, H Sugimura, K Komiya, S |
author_facet | Hirotsu, M Setoguchi, T Matsunoshita, Y Sasaki, H Nagao, H Gao, H Sugimura, K Komiya, S |
author_sort | Hirotsu, M |
collection | PubMed |
description | BACKGROUND: The hypothesis that malignant tumours are generated by rare populations of cancer stem cells that are more tumourigenic than other cancer cells has gained increasing credence. The objective of this study was to identify and characterise a subpopulation of human sarcoma-initiating cells. METHODS: We examined established rhabdomyosarcoma cell lines by flow cytometry. Tumourigenesis was examined by xenograft models. Real-time PCR and immunohistochemistry were performed to examine the gene expression using cell lines and biopsy specimens. RESULTS: Rhabdomyosarcoma cell lines included small populations of fibroblast growth factor receptor 3 (FGFR3)-positive cells. FGFR3-positive KYM-1 and RD cells were more strongly tumourigenic than FGFR3-negative cells. In addition, xenoengraftment of 33% of single FGFR3-positive KYM-1 cells yielded tumour formation. Stem cell properties of FGFR3-positive cells were further established by real-time PCR, which demonstrated upregulation of undifferentiated cell markers and downregulation of differentiation markers. We showed that in the absence of serum, addition of basic fibroblast growth factor maintained and enriched FGFR3-positive cells. On the other hand, ciliary neurotrophic factor reduced the proportion of FGFR3-positive cells. Real-time PCR and immunohistochemical examination revealed that embryonal rhabdomyosarcoma patient biopsy specimens were found to over-express FGFR3. CONCLUSIONS: Our findings suggest that rhabdomyosarcoma cell lines include a minor subpopulation of FGFR3-positive sarcoma-initiating cells, which can be maintained indefinitely in culture and which is crucial for their malignancy. |
format | Text |
id | pubmed-2795447 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-27954472010-12-14 Tumour formation by single fibroblast growth factor receptor 3-positive rhabdomyosarcoma-initiating cells Hirotsu, M Setoguchi, T Matsunoshita, Y Sasaki, H Nagao, H Gao, H Sugimura, K Komiya, S Br J Cancer Molecular Diagnostics BACKGROUND: The hypothesis that malignant tumours are generated by rare populations of cancer stem cells that are more tumourigenic than other cancer cells has gained increasing credence. The objective of this study was to identify and characterise a subpopulation of human sarcoma-initiating cells. METHODS: We examined established rhabdomyosarcoma cell lines by flow cytometry. Tumourigenesis was examined by xenograft models. Real-time PCR and immunohistochemistry were performed to examine the gene expression using cell lines and biopsy specimens. RESULTS: Rhabdomyosarcoma cell lines included small populations of fibroblast growth factor receptor 3 (FGFR3)-positive cells. FGFR3-positive KYM-1 and RD cells were more strongly tumourigenic than FGFR3-negative cells. In addition, xenoengraftment of 33% of single FGFR3-positive KYM-1 cells yielded tumour formation. Stem cell properties of FGFR3-positive cells were further established by real-time PCR, which demonstrated upregulation of undifferentiated cell markers and downregulation of differentiation markers. We showed that in the absence of serum, addition of basic fibroblast growth factor maintained and enriched FGFR3-positive cells. On the other hand, ciliary neurotrophic factor reduced the proportion of FGFR3-positive cells. Real-time PCR and immunohistochemical examination revealed that embryonal rhabdomyosarcoma patient biopsy specimens were found to over-express FGFR3. CONCLUSIONS: Our findings suggest that rhabdomyosarcoma cell lines include a minor subpopulation of FGFR3-positive sarcoma-initiating cells, which can be maintained indefinitely in culture and which is crucial for their malignancy. Nature Publishing Group 2009-12-15 2009-11-03 /pmc/articles/PMC2795447/ /pubmed/19888223 http://dx.doi.org/10.1038/sj.bjc.6605407 Text en Copyright © 2009 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Molecular Diagnostics Hirotsu, M Setoguchi, T Matsunoshita, Y Sasaki, H Nagao, H Gao, H Sugimura, K Komiya, S Tumour formation by single fibroblast growth factor receptor 3-positive rhabdomyosarcoma-initiating cells |
title | Tumour formation by single fibroblast growth factor receptor 3-positive rhabdomyosarcoma-initiating cells |
title_full | Tumour formation by single fibroblast growth factor receptor 3-positive rhabdomyosarcoma-initiating cells |
title_fullStr | Tumour formation by single fibroblast growth factor receptor 3-positive rhabdomyosarcoma-initiating cells |
title_full_unstemmed | Tumour formation by single fibroblast growth factor receptor 3-positive rhabdomyosarcoma-initiating cells |
title_short | Tumour formation by single fibroblast growth factor receptor 3-positive rhabdomyosarcoma-initiating cells |
title_sort | tumour formation by single fibroblast growth factor receptor 3-positive rhabdomyosarcoma-initiating cells |
topic | Molecular Diagnostics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2795447/ https://www.ncbi.nlm.nih.gov/pubmed/19888223 http://dx.doi.org/10.1038/sj.bjc.6605407 |
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