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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2018-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-018-29144-9 |
| _version_ | 1818857731242590208 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T08:45:03Z |
| format | Article |
| id | doaj.art-7c3beab2d533479e8cf1a7cfa2bff92e |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-19T08:45:03Z |
| publishDate | 2018-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-7c3beab2d533479e8cf1a7cfa2bff92e2022-12-21T20:28:49ZengNature PortfolioScientific Reports2045-23222018-07-018111210.1038/s41598-018-29144-9Generation of sphingosine-1-phosphate is enhanced in biliary tract cancer patients and is associated with lymphatic metastasisYuki Hirose0Masayuki Nagahashi1Eriko Katsuta2Kizuki Yuza3Kohei Miura4Jun Sakata5Takashi Kobayashi6Hiroshi Ichikawa7Yoshifumi Shimada8Hitoshi Kameyama9Kerry-Ann McDonald10Kazuaki Takabe11Toshifumi Wakai12Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata CityDivision of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata CityBreast Surgery, Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, BuffaloDivision of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata CityDivision of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata CityDivision of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata CityDivision of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata CityDivision of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata CityDivision of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata CityDivision of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata CityBreast Surgery, Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, BuffaloDivision of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata CityDivision of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata CityAbstract 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.https://doi.org/10.1038/s41598-018-29144-9 |
| spellingShingle | 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 Scientific Reports |
| 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 |
| url | https://doi.org/10.1038/s41598-018-29144-9 |
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