Open Access

4-Methylumbelliferone inhibits enhanced hyaluronan synthesis and cell migration in pancreatic cancer cells in response to tumor-stromal interactions

  • Authors:
    • Xiao‑Bo Cheng
    • Norihiro Sato
    • Shiro Kohi
    • Atsuhiro Koga
    • Keiji Hirata
  • View Affiliations

  • Published online on: March 1, 2018     https://doi.org/10.3892/ol.2018.8147
  • Pages: 6297-6301
  • Copyright: © Cheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.
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May-2018
Volume 15 Issue 5

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Cheng XB, Sato N, Kohi S, Koga A and Hirata K: 4-Methylumbelliferone inhibits enhanced hyaluronan synthesis and cell migration in pancreatic cancer cells in response to tumor-stromal interactions. Oncol Lett 15: 6297-6301, 2018.
APA
Cheng, X., Sato, N., Kohi, S., Koga, A., & Hirata, K. (2018). 4-Methylumbelliferone inhibits enhanced hyaluronan synthesis and cell migration in pancreatic cancer cells in response to tumor-stromal interactions. Oncology Letters, 15, 6297-6301. https://doi.org/10.3892/ol.2018.8147
MLA
Cheng, X., Sato, N., Kohi, S., Koga, A., Hirata, K."4-Methylumbelliferone inhibits enhanced hyaluronan synthesis and cell migration in pancreatic cancer cells in response to tumor-stromal interactions". Oncology Letters 15.5 (2018): 6297-6301.
Chicago
Cheng, X., Sato, N., Kohi, S., Koga, A., Hirata, K."4-Methylumbelliferone inhibits enhanced hyaluronan synthesis and cell migration in pancreatic cancer cells in response to tumor-stromal interactions". Oncology Letters 15, no. 5 (2018): 6297-6301. https://doi.org/10.3892/ol.2018.8147