Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
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
_version_ 1783340303160180736
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
work_keys_str_mv AT hiroseyuki generationofsphingosine1phosphateisenhancedinbiliarytractcancerpatientsandisassociatedwithlymphaticmetastasis
AT nagahashimasayuki generationofsphingosine1phosphateisenhancedinbiliarytractcancerpatientsandisassociatedwithlymphaticmetastasis
AT katsutaeriko generationofsphingosine1phosphateisenhancedinbiliarytractcancerpatientsandisassociatedwithlymphaticmetastasis
AT yuzakizuki generationofsphingosine1phosphateisenhancedinbiliarytractcancerpatientsandisassociatedwithlymphaticmetastasis
AT miurakohei generationofsphingosine1phosphateisenhancedinbiliarytractcancerpatientsandisassociatedwithlymphaticmetastasis
AT sakatajun generationofsphingosine1phosphateisenhancedinbiliarytractcancerpatientsandisassociatedwithlymphaticmetastasis
AT kobayashitakashi generationofsphingosine1phosphateisenhancedinbiliarytractcancerpatientsandisassociatedwithlymphaticmetastasis
AT ichikawahiroshi generationofsphingosine1phosphateisenhancedinbiliarytractcancerpatientsandisassociatedwithlymphaticmetastasis
AT shimadayoshifumi generationofsphingosine1phosphateisenhancedinbiliarytractcancerpatientsandisassociatedwithlymphaticmetastasis
AT kameyamahitoshi generationofsphingosine1phosphateisenhancedinbiliarytractcancerpatientsandisassociatedwithlymphaticmetastasis
AT mcdonaldkerryann generationofsphingosine1phosphateisenhancedinbiliarytractcancerpatientsandisassociatedwithlymphaticmetastasis
AT takabekazuaki generationofsphingosine1phosphateisenhancedinbiliarytractcancerpatientsandisassociatedwithlymphaticmetastasis
AT wakaitoshifumi generationofsphingosine1phosphateisenhancedinbiliarytractcancerpatientsandisassociatedwithlymphaticmetastasis