Metabolomic analysis of small extracellular vesicles derived from pancreatic cancer cells cultured under normoxia and hypoxia

Ryosuke Hayasaka, Sho Tabata, Masako Hasebe, Satsuki Ikeda, Sumiko Ohnuma, Masaru Mori, Tomoyoshi Soga, Masaru Tomita, Akiyoshi Hirayama

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number215
JournalMetabolites
Volume11
Issue number4
DOIs
Publication statusPublished - 2021 Apr

Keywords

  • Capillary ion chromatography-mass spectrometry
  • Hypoxia
  • Liquid chromatography-mass spectrometry
  • Metabolome analysis
  • Pancreatic cancer
  • Small extracellular vesicles
  • Supercritical fluid chromatography-tandem mass spectrometry

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology

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