Metabolomic Analysis of Small Extracellular Vesicles Derived from Pancreatic Cancer Cells Cultured under Normoxia and Hypoxia
Extracellular vesicles (EVs) released from cancer cells contribute to various malignant phenotypes of cancer, including metastasis, cachexia, and angiogenesis. Although DNA, mRNAs, miRNAs, and proteins contained in EVs have been extensively studied, the function of metabolites in EVs remains unclear...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-04-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/11/4/215 |
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| author | Ryosuke Hayasaka Sho Tabata Masako Hasebe Satsuki Ikeda Sumiko Ohnuma Masaru Mori Tomoyoshi Soga Masaru Tomita Akiyoshi Hirayama |
| author_facet | Ryosuke Hayasaka Sho Tabata Masako Hasebe Satsuki Ikeda Sumiko Ohnuma Masaru Mori Tomoyoshi Soga Masaru Tomita Akiyoshi Hirayama |
| author_sort | Ryosuke Hayasaka |
| collection | DOAJ |
| description | Extracellular vesicles (EVs) released from cancer cells contribute to various malignant phenotypes of cancer, including metastasis, cachexia, and angiogenesis. Although DNA, mRNAs, miRNAs, and proteins contained in EVs have been extensively studied, the function of metabolites in EVs remains unclear. In this study, we performed a comprehensive metabolomic analysis of pancreatic cancer cells, PANC-1, cultured under different oxygen concentrations, and small EVs (sEVs) released from them, considering the fact that hypoxia contributes to the malignant behavior of cells in pancreatic cancer, which is a poorly diagnosed cancer. sEVs were collected by ultracentrifugation, and hydrophilic metabolites were analyzed using capillary ion chromatography-mass spectrometry and liquid chromatography-mass spectrometry, and lipids were analyzed by supercritical fluid chromatography-tandem mass spectrometry. A total of 140 hydrophilic metabolites and 494 lipids were detected in sEVs, and their profiles were different from those in cells. In addition, the metabolomic profile of sEVs was observed to change under hypoxic stress, and an increase in metabolites involved in angiogenesis was also detected. We reveal the hallmark of the metabolites contained in sEVs and the effect of tumor hypoxia on their profiles, which may help in understanding EV-mediated cancer malignancy. |
| first_indexed | 2024-03-10T12:42:12Z |
| format | Article |
| id | doaj.art-0f0ff76cf8c44d8186b6440f1d71956f |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-10T12:42:12Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-0f0ff76cf8c44d8186b6440f1d71956f2023-11-21T13:46:15ZengMDPI AGMetabolites2218-19892021-04-0111421510.3390/metabo11040215Metabolomic Analysis of Small Extracellular Vesicles Derived from Pancreatic Cancer Cells Cultured under Normoxia and HypoxiaRyosuke Hayasaka0Sho Tabata1Masako Hasebe2Satsuki Ikeda3Sumiko Ohnuma4Masaru Mori5Tomoyoshi Soga6Masaru Tomita7Akiyoshi Hirayama8Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, JapanInstitute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, JapanInstitute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, JapanInstitute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, JapanInstitute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, JapanInstitute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, JapanInstitute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, JapanInstitute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, JapanInstitute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, JapanExtracellular vesicles (EVs) released from cancer cells contribute to various malignant phenotypes of cancer, including metastasis, cachexia, and angiogenesis. Although DNA, mRNAs, miRNAs, and proteins contained in EVs have been extensively studied, the function of metabolites in EVs remains unclear. In this study, we performed a comprehensive metabolomic analysis of pancreatic cancer cells, PANC-1, cultured under different oxygen concentrations, and small EVs (sEVs) released from them, considering the fact that hypoxia contributes to the malignant behavior of cells in pancreatic cancer, which is a poorly diagnosed cancer. sEVs were collected by ultracentrifugation, and hydrophilic metabolites were analyzed using capillary ion chromatography-mass spectrometry and liquid chromatography-mass spectrometry, and lipids were analyzed by supercritical fluid chromatography-tandem mass spectrometry. A total of 140 hydrophilic metabolites and 494 lipids were detected in sEVs, and their profiles were different from those in cells. In addition, the metabolomic profile of sEVs was observed to change under hypoxic stress, and an increase in metabolites involved in angiogenesis was also detected. We reveal the hallmark of the metabolites contained in sEVs and the effect of tumor hypoxia on their profiles, which may help in understanding EV-mediated cancer malignancy.https://www.mdpi.com/2218-1989/11/4/215small extracellular vesiclesmetabolome analysispancreatic cancerhypoxiacapillary ion chromatography-mass spectrometryliquid chromatography-mass spectrometry |
| spellingShingle | Ryosuke Hayasaka Sho Tabata Masako Hasebe Satsuki Ikeda Sumiko Ohnuma Masaru Mori Tomoyoshi Soga Masaru Tomita Akiyoshi Hirayama Metabolomic Analysis of Small Extracellular Vesicles Derived from Pancreatic Cancer Cells Cultured under Normoxia and Hypoxia Metabolites small extracellular vesicles metabolome analysis pancreatic cancer hypoxia capillary ion chromatography-mass spectrometry liquid chromatography-mass spectrometry |
| title | Metabolomic Analysis of Small Extracellular Vesicles Derived from Pancreatic Cancer Cells Cultured under Normoxia and Hypoxia |
| title_full | Metabolomic Analysis of Small Extracellular Vesicles Derived from Pancreatic Cancer Cells Cultured under Normoxia and Hypoxia |
| title_fullStr | Metabolomic Analysis of Small Extracellular Vesicles Derived from Pancreatic Cancer Cells Cultured under Normoxia and Hypoxia |
| title_full_unstemmed | Metabolomic Analysis of Small Extracellular Vesicles Derived from Pancreatic Cancer Cells Cultured under Normoxia and Hypoxia |
| title_short | Metabolomic Analysis of Small Extracellular Vesicles Derived from Pancreatic Cancer Cells Cultured under Normoxia and Hypoxia |
| title_sort | metabolomic analysis of small extracellular vesicles derived from pancreatic cancer cells cultured under normoxia and hypoxia |
| topic | small extracellular vesicles metabolome analysis pancreatic cancer hypoxia capillary ion chromatography-mass spectrometry liquid chromatography-mass spectrometry |
| url | https://www.mdpi.com/2218-1989/11/4/215 |
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