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Fascin-1 enhances experimental osteosarcoma tumor formation and metastasis and is related to poor patient outcome
BACKGROUND: Fascin-1, a prominent actin-bundling protein, is found to be upregulated in several human carcinomas. While it is accepted that Fascin-1 expression correlates with poor clinical outcome and decreased survival in various carcinomas, its role in sarcoma such as osteosarcoma (OS) remains un...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6337773/ https://www.ncbi.nlm.nih.gov/pubmed/30654764 http://dx.doi.org/10.1186/s12885-019-5303-3 |
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author | Arlt, Matthias J. Kuzmanov, Aleksandar Snedeker, Jess G. Fuchs, Bruno Silvan, Unai Sabile, Adam A. |
author_facet | Arlt, Matthias J. Kuzmanov, Aleksandar Snedeker, Jess G. Fuchs, Bruno Silvan, Unai Sabile, Adam A. |
author_sort | Arlt, Matthias J. |
collection | PubMed |
description | BACKGROUND: Fascin-1, a prominent actin-bundling protein, is found to be upregulated in several human carcinomas. While it is accepted that Fascin-1 expression correlates with poor clinical outcome and decreased survival in various carcinomas, its role in sarcoma such as osteosarcoma (OS) remains unknown. In the present study, we evaluated the prognostic value and biological relevance of Fascin-1 in OS. METHODS: The correlation between Fascin-1 expression and the outcome of OS patients was determined by immunohistochemistry analysis of Fascin-1 expression in a tissue microarray of OS tissue specimens collected during primary tumor resection. To examine the effect of Fascin-1, shRNA and overexpression technology to alter Fascin-1 levels in OS cells were used in cellular assays as well as in intratibial xenograft OS models in SCID mice. RESULTS: Kaplan-Meier survival analysis of Fascin-1 expression in OS tumor specimens revealed a direct relationship between Fascin-1 expression and poor patient survival. Furthermore, overexpression of Fascin-1 in OS cells significantly increased their migratory capacity as well as the activity of the matrix metalloprotease MMP-9, known to be critical for the execution of metastasis. Finally, using relevant xenograft mouse models, orthotopic intratibial transplantation of two different OS cell lines overexpressing Fascin-1 promoted tumor growth and lung metastasis. CONCLUSIONS: Collectively, our findings demonstrate for the first time that Fascin-1 has considerable potential as a novel prognostic biomarker in OS, and suggest that targeting of Fascin-1 might be a new anti-metastatic strategy in OS patient treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-019-5303-3) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6337773 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-63377732019-01-23 Fascin-1 enhances experimental osteosarcoma tumor formation and metastasis and is related to poor patient outcome Arlt, Matthias J. Kuzmanov, Aleksandar Snedeker, Jess G. Fuchs, Bruno Silvan, Unai Sabile, Adam A. BMC Cancer Research Article BACKGROUND: Fascin-1, a prominent actin-bundling protein, is found to be upregulated in several human carcinomas. While it is accepted that Fascin-1 expression correlates with poor clinical outcome and decreased survival in various carcinomas, its role in sarcoma such as osteosarcoma (OS) remains unknown. In the present study, we evaluated the prognostic value and biological relevance of Fascin-1 in OS. METHODS: The correlation between Fascin-1 expression and the outcome of OS patients was determined by immunohistochemistry analysis of Fascin-1 expression in a tissue microarray of OS tissue specimens collected during primary tumor resection. To examine the effect of Fascin-1, shRNA and overexpression technology to alter Fascin-1 levels in OS cells were used in cellular assays as well as in intratibial xenograft OS models in SCID mice. RESULTS: Kaplan-Meier survival analysis of Fascin-1 expression in OS tumor specimens revealed a direct relationship between Fascin-1 expression and poor patient survival. Furthermore, overexpression of Fascin-1 in OS cells significantly increased their migratory capacity as well as the activity of the matrix metalloprotease MMP-9, known to be critical for the execution of metastasis. Finally, using relevant xenograft mouse models, orthotopic intratibial transplantation of two different OS cell lines overexpressing Fascin-1 promoted tumor growth and lung metastasis. CONCLUSIONS: Collectively, our findings demonstrate for the first time that Fascin-1 has considerable potential as a novel prognostic biomarker in OS, and suggest that targeting of Fascin-1 might be a new anti-metastatic strategy in OS patient treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-019-5303-3) contains supplementary material, which is available to authorized users. BioMed Central 2019-01-17 /pmc/articles/PMC6337773/ /pubmed/30654764 http://dx.doi.org/10.1186/s12885-019-5303-3 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Arlt, Matthias J. Kuzmanov, Aleksandar Snedeker, Jess G. Fuchs, Bruno Silvan, Unai Sabile, Adam A. Fascin-1 enhances experimental osteosarcoma tumor formation and metastasis and is related to poor patient outcome |
title | Fascin-1 enhances experimental osteosarcoma tumor formation and metastasis and is related to poor patient outcome |
title_full | Fascin-1 enhances experimental osteosarcoma tumor formation and metastasis and is related to poor patient outcome |
title_fullStr | Fascin-1 enhances experimental osteosarcoma tumor formation and metastasis and is related to poor patient outcome |
title_full_unstemmed | Fascin-1 enhances experimental osteosarcoma tumor formation and metastasis and is related to poor patient outcome |
title_short | Fascin-1 enhances experimental osteosarcoma tumor formation and metastasis and is related to poor patient outcome |
title_sort | fascin-1 enhances experimental osteosarcoma tumor formation and metastasis and is related to poor patient outcome |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6337773/ https://www.ncbi.nlm.nih.gov/pubmed/30654764 http://dx.doi.org/10.1186/s12885-019-5303-3 |
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