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Generation of sphingosine-1-phosphate is enhanced in biliary tract cancer patients and is associated with lymphatic metastasis
Lymphatic metastasis is known to contribute to worse prognosis of biliary tract cancer (BTC). Recently, sphingosine-1-phosphate (S1P), a bioactive lipid mediator generated by sphingosine kinase 1 (SPHK1), has been shown to play an important role in lymphangiogenesis and lymph node metastasis in seve...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6050292/ https://www.ncbi.nlm.nih.gov/pubmed/30018456 http://dx.doi.org/10.1038/s41598-018-29144-9 |
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author | Hirose, Yuki Nagahashi, Masayuki Katsuta, Eriko Yuza, Kizuki Miura, Kohei Sakata, Jun Kobayashi, Takashi Ichikawa, Hiroshi Shimada, Yoshifumi Kameyama, Hitoshi McDonald, Kerry-Ann Takabe, Kazuaki Wakai, Toshifumi |
author_facet | Hirose, Yuki Nagahashi, Masayuki Katsuta, Eriko Yuza, Kizuki Miura, Kohei Sakata, Jun Kobayashi, Takashi Ichikawa, Hiroshi Shimada, Yoshifumi Kameyama, Hitoshi McDonald, Kerry-Ann Takabe, Kazuaki Wakai, Toshifumi |
author_sort | Hirose, Yuki |
collection | PubMed |
description | Lymphatic metastasis is known to contribute to worse prognosis of biliary tract cancer (BTC). Recently, sphingosine-1-phosphate (S1P), a bioactive lipid mediator generated by sphingosine kinase 1 (SPHK1), has been shown to play an important role in lymphangiogenesis and lymph node metastasis in several types of cancer. However, the role of the lipid mediator in BTC has never been examined. Here we found that S1P is elevated in BTC with the activation of ceramide-synthetic pathways, suggesting that BTC utilizes SPHK1 to promote lymphatic metastasis. We found that S1P, sphingosine and ceramide precursors such as monohexosyl-ceramide and sphingomyelin, but not ceramide, were significantly increased in BTC compared to normal biliary tract tissue using LC-ESI-MS/MS. Utilizing The Cancer Genome Atlas cohort, we demonstrated that S1P in BTC is generated via de novo pathway and exported via ABCC1. Further, we found that SPHK1 expression positively correlated with factors related to lymphatic metastasis in BTC. Finally, immunohistochemical examination revealed that gallbladder cancer with lymph node metastasis had significantly higher expression of phospho-SPHK1 than that without. Taken together, our data suggest that S1P generated in BTC contributes to lymphatic metastasis. |
format | Online Article Text |
id | pubmed-6050292 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-60502922018-07-19 Generation of sphingosine-1-phosphate is enhanced in biliary tract cancer patients and is associated with lymphatic metastasis Hirose, Yuki Nagahashi, Masayuki Katsuta, Eriko Yuza, Kizuki Miura, Kohei Sakata, Jun Kobayashi, Takashi Ichikawa, Hiroshi Shimada, Yoshifumi Kameyama, Hitoshi McDonald, Kerry-Ann Takabe, Kazuaki Wakai, Toshifumi Sci Rep Article Lymphatic metastasis is known to contribute to worse prognosis of biliary tract cancer (BTC). Recently, sphingosine-1-phosphate (S1P), a bioactive lipid mediator generated by sphingosine kinase 1 (SPHK1), has been shown to play an important role in lymphangiogenesis and lymph node metastasis in several types of cancer. However, the role of the lipid mediator in BTC has never been examined. Here we found that S1P is elevated in BTC with the activation of ceramide-synthetic pathways, suggesting that BTC utilizes SPHK1 to promote lymphatic metastasis. We found that S1P, sphingosine and ceramide precursors such as monohexosyl-ceramide and sphingomyelin, but not ceramide, were significantly increased in BTC compared to normal biliary tract tissue using LC-ESI-MS/MS. Utilizing The Cancer Genome Atlas cohort, we demonstrated that S1P in BTC is generated via de novo pathway and exported via ABCC1. Further, we found that SPHK1 expression positively correlated with factors related to lymphatic metastasis in BTC. Finally, immunohistochemical examination revealed that gallbladder cancer with lymph node metastasis had significantly higher expression of phospho-SPHK1 than that without. Taken together, our data suggest that S1P generated in BTC contributes to lymphatic metastasis. Nature Publishing Group UK 2018-07-17 /pmc/articles/PMC6050292/ /pubmed/30018456 http://dx.doi.org/10.1038/s41598-018-29144-9 Text en © The Author(s) 2018 Open Access 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 http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Hirose, Yuki Nagahashi, Masayuki Katsuta, Eriko Yuza, Kizuki Miura, Kohei Sakata, Jun Kobayashi, Takashi Ichikawa, Hiroshi Shimada, Yoshifumi Kameyama, Hitoshi McDonald, Kerry-Ann Takabe, Kazuaki Wakai, Toshifumi Generation of sphingosine-1-phosphate is enhanced in biliary tract cancer patients and is associated with lymphatic metastasis |
title | Generation of sphingosine-1-phosphate is enhanced in biliary tract cancer patients and is associated with lymphatic metastasis |
title_full | Generation of sphingosine-1-phosphate is enhanced in biliary tract cancer patients and is associated with lymphatic metastasis |
title_fullStr | Generation of sphingosine-1-phosphate is enhanced in biliary tract cancer patients and is associated with lymphatic metastasis |
title_full_unstemmed | Generation of sphingosine-1-phosphate is enhanced in biliary tract cancer patients and is associated with lymphatic metastasis |
title_short | Generation of sphingosine-1-phosphate is enhanced in biliary tract cancer patients and is associated with lymphatic metastasis |
title_sort | generation of sphingosine-1-phosphate is enhanced in biliary tract cancer patients and is associated with lymphatic metastasis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6050292/ https://www.ncbi.nlm.nih.gov/pubmed/30018456 http://dx.doi.org/10.1038/s41598-018-29144-9 |
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