TY - JOUR
T1 - Metabolomic analysis of small extracellular vesicles derived from pancreatic cancer cells cultured under normoxia and hypoxia
AU - Hayasaka, Ryosuke
AU - Tabata, Sho
AU - Hasebe, Masako
AU - Ikeda, Satsuki
AU - Ohnuma, Sumiko
AU - Mori, Masaru
AU - Soga, Tomoyoshi
AU - Tomita, Masaru
AU - Hirayama, Akiyoshi
N1 - Funding Information:
Funding: This research was funded by JSPS KAKENHI grant numbers JP20J12816 (R.H.), JP18H04804 (A.H.), and JP18K08219 (A.H.); Research on Development of New Drugs (GAPFREE) from the Japan Agency for Medical Research and Development, AMED grant numbers 18ak0101043h0104, 18ak0101043s1404, and 18ak0101043h0004 (A.H.); Taikichiro Mori Memorial Research Grants (R.H.), and grants from the Yamagata prefectural government and the city of Tsuruoka.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/4
Y1 - 2021/4
N2 - 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 ultracen-trifugation, and hydrophilic metabolites were analyzed using capillary ion chromatography-mass spectrometry and liquid chromatography-mass spectrometry, and lipids were analyzed by supercrit-ical 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.
AB - 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 ultracen-trifugation, and hydrophilic metabolites were analyzed using capillary ion chromatography-mass spectrometry and liquid chromatography-mass spectrometry, and lipids were analyzed by supercrit-ical 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.
KW - Capillary ion chromatography-mass spectrometry
KW - Hypoxia
KW - Liquid chromatography-mass spectrometry
KW - Metabolome analysis
KW - Pancreatic cancer
KW - Small extracellular vesicles
KW - Supercritical fluid chromatography-tandem mass spectrometry
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U2 - 10.3390/metabo11040215
DO - 10.3390/metabo11040215
M3 - Article
AN - SCOPUS:85104323653
SN - 2218-1989
VL - 11
JO - Metabolites
JF - Metabolites
IS - 4
M1 - 215
ER -
