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Metabolomic Analysis of Small Extracellular Vesicles Derived from Pancreatic Cancer Cells Cultured under Normoxia and Hypoxia

1
Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, Japan
2
Systems Biology Program, Graduate School of Media and Governance, Keio University, Fujisawa, Kanagawa 252-0882, Japan
3
Institute for Protein Research, Osaka University, Suita, Osaka 565-0871, Japan
4
Institute of Nano-Life-Systems, Institutes of Innovation for Future Society, Nagoya University, Nagoya, Aichi 464-8603, Japan
*
Author to whom correspondence should be addressed.
Academic Editor: James McCullagh
Metabolites 2021, 11(4), 215; https://doi.org/10.3390/metabo11040215
Received: 8 February 2021 / Revised: 23 March 2021 / Accepted: 29 March 2021 / Published: 1 April 2021
(This article belongs to the Section Cell Metabolism)
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. View Full-Text
Keywords: small extracellular vesicles; metabolome analysis; pancreatic cancer; hypoxia; capillary ion chromatography-mass spectrometry; liquid chromatography-mass spectrometry; supercritical fluid chromatography-tandem mass spectrometry small extracellular vesicles; metabolome analysis; pancreatic cancer; hypoxia; capillary ion chromatography-mass spectrometry; liquid chromatography-mass spectrometry; supercritical fluid chromatography-tandem mass spectrometry
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MDPI and ACS Style

Hayasaka, R.; Tabata, S.; Hasebe, M.; Ikeda, S.; Ohnuma, S.; Mori, M.; Soga, T.; Tomita, M.; Hirayama, A. Metabolomic Analysis of Small Extracellular Vesicles Derived from Pancreatic Cancer Cells Cultured under Normoxia and Hypoxia. Metabolites 2021, 11, 215. https://doi.org/10.3390/metabo11040215

AMA Style

Hayasaka R, Tabata S, Hasebe M, Ikeda S, Ohnuma S, Mori M, Soga T, Tomita M, Hirayama A. Metabolomic Analysis of Small Extracellular Vesicles Derived from Pancreatic Cancer Cells Cultured under Normoxia and Hypoxia. Metabolites. 2021; 11(4):215. https://doi.org/10.3390/metabo11040215

Chicago/Turabian Style

Hayasaka, Ryosuke; Tabata, Sho; Hasebe, Masako; Ikeda, Satsuki; Ohnuma, Sumiko; Mori, Masaru; Soga, Tomoyoshi; Tomita, Masaru; Hirayama, Akiyoshi. 2021. "Metabolomic Analysis of Small Extracellular Vesicles Derived from Pancreatic Cancer Cells Cultured under Normoxia and Hypoxia" Metabolites 11, no. 4: 215. https://doi.org/10.3390/metabo11040215

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