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BMP-2 Promotes Oral Squamous Carcinoma Cell Invasion by Inducing CCL5 Release
Bone morphogenetic protein-2 (BMP-2)-containing bone grafts are useful regenerative materials for oral and maxillofacial surgery; however, several in vitro and in vivo studies previously reported cancer progression-related adverse effects caused by BMP-2. In this study, by quantifying the rhBMP-2 co...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182698/ https://www.ncbi.nlm.nih.gov/pubmed/25271422 http://dx.doi.org/10.1371/journal.pone.0108170 |
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author | Kim, Mi-joo Kim, Kwang-mahn Kim, Jin Kim, Kyoung-nam |
author_facet | Kim, Mi-joo Kim, Kwang-mahn Kim, Jin Kim, Kyoung-nam |
author_sort | Kim, Mi-joo |
collection | PubMed |
description | Bone morphogenetic protein-2 (BMP-2)-containing bone grafts are useful regenerative materials for oral and maxillofacial surgery; however, several in vitro and in vivo studies previously reported cancer progression-related adverse effects caused by BMP-2. In this study, by quantifying the rhBMP-2 content released from bone grafts, the rhBMP-2 concentration that did not show cytotoxicity in each cell line was determined and applied to the in vitro monoculture or coculture model in the invasion assay. Our results showed that 1 ng/ml rhBMP-2, while not affecting cancer cell viability, significantly increased the invasion ability of the cancer cells cocultured with fibroblasts. Cocultured medium with rhBMP-2 also contained increased levels of matrix metalloproteinases. rhBMP-2-treated cocultured fibroblasts did not show a prominent difference in mRNA expression profile. Some cytokines, however, were detected in the conditioned medium by a human cytokine antibody array. Among them, the cancer invasion-related factor CCL5 was quantified by ELISA. Interestingly, CCL5 neutralizing antibodies significantly reduced the invasion of oral cancer cells. In conclusion, our results suggest that 1 ng/ml rhBMP-2 may induce invasion of oral squamous cell carcinoma (OSCC) cells by CCL5 release in coculture models. Therefore, we propose that a careful clinical examination before the use of rhBMP-2-containing biomaterials is indispensable for using rhBMP-2 treatment to prevent cancer progression. |
format | Online Article Text |
id | pubmed-4182698 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-41826982014-10-07 BMP-2 Promotes Oral Squamous Carcinoma Cell Invasion by Inducing CCL5 Release Kim, Mi-joo Kim, Kwang-mahn Kim, Jin Kim, Kyoung-nam PLoS One Research Article Bone morphogenetic protein-2 (BMP-2)-containing bone grafts are useful regenerative materials for oral and maxillofacial surgery; however, several in vitro and in vivo studies previously reported cancer progression-related adverse effects caused by BMP-2. In this study, by quantifying the rhBMP-2 content released from bone grafts, the rhBMP-2 concentration that did not show cytotoxicity in each cell line was determined and applied to the in vitro monoculture or coculture model in the invasion assay. Our results showed that 1 ng/ml rhBMP-2, while not affecting cancer cell viability, significantly increased the invasion ability of the cancer cells cocultured with fibroblasts. Cocultured medium with rhBMP-2 also contained increased levels of matrix metalloproteinases. rhBMP-2-treated cocultured fibroblasts did not show a prominent difference in mRNA expression profile. Some cytokines, however, were detected in the conditioned medium by a human cytokine antibody array. Among them, the cancer invasion-related factor CCL5 was quantified by ELISA. Interestingly, CCL5 neutralizing antibodies significantly reduced the invasion of oral cancer cells. In conclusion, our results suggest that 1 ng/ml rhBMP-2 may induce invasion of oral squamous cell carcinoma (OSCC) cells by CCL5 release in coculture models. Therefore, we propose that a careful clinical examination before the use of rhBMP-2-containing biomaterials is indispensable for using rhBMP-2 treatment to prevent cancer progression. Public Library of Science 2014-10-01 /pmc/articles/PMC4182698/ /pubmed/25271422 http://dx.doi.org/10.1371/journal.pone.0108170 Text en © 2014 Kim 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 Kim, Mi-joo Kim, Kwang-mahn Kim, Jin Kim, Kyoung-nam BMP-2 Promotes Oral Squamous Carcinoma Cell Invasion by Inducing CCL5 Release |
title | BMP-2 Promotes Oral Squamous Carcinoma Cell Invasion by Inducing CCL5 Release |
title_full | BMP-2 Promotes Oral Squamous Carcinoma Cell Invasion by Inducing CCL5 Release |
title_fullStr | BMP-2 Promotes Oral Squamous Carcinoma Cell Invasion by Inducing CCL5 Release |
title_full_unstemmed | BMP-2 Promotes Oral Squamous Carcinoma Cell Invasion by Inducing CCL5 Release |
title_short | BMP-2 Promotes Oral Squamous Carcinoma Cell Invasion by Inducing CCL5 Release |
title_sort | bmp-2 promotes oral squamous carcinoma cell invasion by inducing ccl5 release |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182698/ https://www.ncbi.nlm.nih.gov/pubmed/25271422 http://dx.doi.org/10.1371/journal.pone.0108170 |
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