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4-Methylumbelliferone inhibits enhanced hyaluronan synthesis and cell migration in pancreatic cancer cells in response to tumor-stromal interactions
Hyaluronic acid (HA) in tumor stroma promotes tumor invasion and progression. 4-Methylumbelliferone (4-MU) is a potent HA synthesis inhibitor. In the present study, the effects of 4-MU on enhanced HA synthesis and cell migration in pancreatic ductal adenocarcinoma (PDAC) cells, in response to co-cul...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5920249/ https://www.ncbi.nlm.nih.gov/pubmed/29725394 http://dx.doi.org/10.3892/ol.2018.8147 |
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author | Cheng, Xiao-Bo Sato, Norihiro Kohi, Shiro Koga, Atsuhiro Hirata, Keiji |
author_facet | Cheng, Xiao-Bo Sato, Norihiro Kohi, Shiro Koga, Atsuhiro Hirata, Keiji |
author_sort | Cheng, Xiao-Bo |
collection | PubMed |
description | Hyaluronic acid (HA) in tumor stroma promotes tumor invasion and progression. 4-Methylumbelliferone (4-MU) is a potent HA synthesis inhibitor. In the present study, the effects of 4-MU on enhanced HA synthesis and cell migration in pancreatic ductal adenocarcinoma (PDAC) cells, in response to co-culture with stromal fibroblasts, was investigated. The HA concentration was determined using ELISA and a Transwell migration assay was used to analyze cell migratory capability. The mRNA expression levels of hyaluronan synthases (HAS1, HAS2 and HAS3) were determined using the quantitative polymerase chain reaction. Co-culture between Panc-1 cells and stromal fibroblasts markedly increased cell migration in association with increasing HA production, which was markedly associated with an increase in HAS3 mRNA expression. Treatment with 4-MU markedly decreased the HA production and cell migration of Panc-1 cells in the co-culture system. The results of the present study suggested that interactions between PDAC cells and stromal fibroblasts increased HA production, resulting in a marked increase in migration of PDAC cells, and 4-MU may be used as a chemotherapeutic agent to inhibit the enhanced migration of PDAC cells in response to tumor-stromal interactions. |
format | Online Article Text |
id | pubmed-5920249 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-59202492018-05-03 4-Methylumbelliferone inhibits enhanced hyaluronan synthesis and cell migration in pancreatic cancer cells in response to tumor-stromal interactions Cheng, Xiao-Bo Sato, Norihiro Kohi, Shiro Koga, Atsuhiro Hirata, Keiji Oncol Lett Articles Hyaluronic acid (HA) in tumor stroma promotes tumor invasion and progression. 4-Methylumbelliferone (4-MU) is a potent HA synthesis inhibitor. In the present study, the effects of 4-MU on enhanced HA synthesis and cell migration in pancreatic ductal adenocarcinoma (PDAC) cells, in response to co-culture with stromal fibroblasts, was investigated. The HA concentration was determined using ELISA and a Transwell migration assay was used to analyze cell migratory capability. The mRNA expression levels of hyaluronan synthases (HAS1, HAS2 and HAS3) were determined using the quantitative polymerase chain reaction. Co-culture between Panc-1 cells and stromal fibroblasts markedly increased cell migration in association with increasing HA production, which was markedly associated with an increase in HAS3 mRNA expression. Treatment with 4-MU markedly decreased the HA production and cell migration of Panc-1 cells in the co-culture system. The results of the present study suggested that interactions between PDAC cells and stromal fibroblasts increased HA production, resulting in a marked increase in migration of PDAC cells, and 4-MU may be used as a chemotherapeutic agent to inhibit the enhanced migration of PDAC cells in response to tumor-stromal interactions. D.A. Spandidos 2018-05 2018-03-01 /pmc/articles/PMC5920249/ /pubmed/29725394 http://dx.doi.org/10.3892/ol.2018.8147 Text en Copyright: © Cheng et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Cheng, Xiao-Bo Sato, Norihiro Kohi, Shiro Koga, Atsuhiro Hirata, Keiji 4-Methylumbelliferone inhibits enhanced hyaluronan synthesis and cell migration in pancreatic cancer cells in response to tumor-stromal interactions |
title | 4-Methylumbelliferone inhibits enhanced hyaluronan synthesis and cell migration in pancreatic cancer cells in response to tumor-stromal interactions |
title_full | 4-Methylumbelliferone inhibits enhanced hyaluronan synthesis and cell migration in pancreatic cancer cells in response to tumor-stromal interactions |
title_fullStr | 4-Methylumbelliferone inhibits enhanced hyaluronan synthesis and cell migration in pancreatic cancer cells in response to tumor-stromal interactions |
title_full_unstemmed | 4-Methylumbelliferone inhibits enhanced hyaluronan synthesis and cell migration in pancreatic cancer cells in response to tumor-stromal interactions |
title_short | 4-Methylumbelliferone inhibits enhanced hyaluronan synthesis and cell migration in pancreatic cancer cells in response to tumor-stromal interactions |
title_sort | 4-methylumbelliferone inhibits enhanced hyaluronan synthesis and cell migration in pancreatic cancer cells in response to tumor-stromal interactions |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5920249/ https://www.ncbi.nlm.nih.gov/pubmed/29725394 http://dx.doi.org/10.3892/ol.2018.8147 |
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