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Mass Spectrometry Reveals High Levels of Hydrogen Peroxide in Pancreatic Cancer Cells
Authors:Qinlei Liu  Dr Wenjie Ge  Dr Sandra Martínez-Jarquín  Yuliang He  Dr Ri Wu  Prof Dr Markus Stoffel  Prof Dr Renato Zenobi
Institution:1. Department of Chemistry and Applied Biosciences, ETH Zurich, Vladimir-Prelog-Weg 3, 8093 Zurich, Switzerland

These authors contributed equally to this work.;2. Department of Biology, ETH Zurich, Otto-Stern-Weg 7, 8093 Zurich, Switzerland

Current address: Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, 221004 China

These authors contributed equally to this work.;3. Department of Chemistry and Applied Biosciences, ETH Zurich, Vladimir-Prelog-Weg 3, 8093 Zurich, Switzerland;4. Department of Biology, ETH Zurich, Otto-Stern-Weg 7, 8093 Zurich, Switzerland

Abstract:Reactive oxygen species (ROS) are critical for many cellular functions, and dysregulation of ROS involves the development of multiple types of tumors, including pancreatic cancer. However, ROS have been grouped into a single biochemical entity for a long time, and the specific roles of certain types of ROS in tumor cells (e.g., pancreatic ductal adenocarcinoma (PDAC)) have not been systematically investigated. In this work, a highly sensitive and accurate mass spectrometry-based method was applied to study PDAC cells of humans and of genetically modified animals. The results show that the oncogenic KRAS mutation promotes the accumulation of hydrogen peroxide (H2O2) rather than superoxide or hydroxyl radicals in pancreatic cancer cells. We further identified that the enriched H2O2 modifies cellular metabolites and promotes the survival of pancreatic cancer cells. These findings highlight the specific roles of H2O2 in pancreatic cancer development, which may provide new directions for pancreatic cancer therapy.
Keywords:ESI-MS  Hydrogen Peroxide  Metabolic Changes  Pancreatic Cancer  Reactive Oxygen Species
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