Generation of sphingosine-1-phosphate is enhanced in biliary tract cancer patients and is associated with lymphatic metastasis

Abstract 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 metastasi...

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Autores principales:	Yuki Hirose, Masayuki Nagahashi, Eriko Katsuta, Kizuki Yuza, Kohei Miura, Jun Sakata, Takashi Kobayashi, Hiroshi Ichikawa, Yoshifumi Shimada, Hitoshi Kameyama, Kerry-Ann McDonald, Kazuaki Takabe, Toshifumi Wakai
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7c3beab2d533479e8cf1a7cfa2bff92e
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spelling	oai:doaj.org-article:7c3beab2d533479e8cf1a7cfa2bff92e2021-12-02T11:40:47ZGeneration of sphingosine-1-phosphate is enhanced in biliary tract cancer patients and is associated with lymphatic metastasis10.1038/s41598-018-29144-92045-2322https://doaj.org/article/7c3beab2d533479e8cf1a7cfa2bff92e2018-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-29144-9https://doaj.org/toc/2045-2322Abstract 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.Yuki HiroseMasayuki NagahashiEriko KatsutaKizuki YuzaKohei MiuraJun SakataTakashi KobayashiHiroshi IchikawaYoshifumi ShimadaHitoshi KameyamaKerry-Ann McDonaldKazuaki TakabeToshifumi WakaiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-12 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yuki Hirose Masayuki Nagahashi Eriko Katsuta Kizuki Yuza Kohei Miura Jun Sakata Takashi Kobayashi Hiroshi Ichikawa Yoshifumi Shimada Hitoshi Kameyama Kerry-Ann McDonald Kazuaki Takabe Toshifumi Wakai Generation of sphingosine-1-phosphate is enhanced in biliary tract cancer patients and is associated with lymphatic metastasis
description	Abstract 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	article
author	Yuki Hirose Masayuki Nagahashi Eriko Katsuta Kizuki Yuza Kohei Miura Jun Sakata Takashi Kobayashi Hiroshi Ichikawa Yoshifumi Shimada Hitoshi Kameyama Kerry-Ann McDonald Kazuaki Takabe Toshifumi Wakai
author_facet	Yuki Hirose Masayuki Nagahashi Eriko Katsuta Kizuki Yuza Kohei Miura Jun Sakata Takashi Kobayashi Hiroshi Ichikawa Yoshifumi Shimada Hitoshi Kameyama Kerry-Ann McDonald Kazuaki Takabe Toshifumi Wakai
author_sort	Yuki Hirose
title	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_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_sort	generation of sphingosine-1-phosphate is enhanced in biliary tract cancer patients and is associated with lymphatic metastasis
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/7c3beab2d533479e8cf1a7cfa2bff92e
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Generation of sphingosine-1-phosphate is enhanced in biliary tract cancer patients and is associated with lymphatic metastasis

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