Cell-selective proteomics segregates pancreatic cancer subtypes by extracellular proteins in tumors and circulation.

Autor: Swietlik JJ; Experimental Systems Immunology, Max Planck Institute of Biochemistry, Martinsried, Germany., Bärthel S; Division of Translational Cancer Research, German Cancer Research Center and German Cancer Consortium, Heidelberg, Germany.; Chair of Translational Cancer Research and Institute of Experimental Cancer Therapy, University Hospital Rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany.; Center for Translational Cancer Research (TranslaTUM), School of Medicine, Technical University of Munich, Munich, Germany., Falcomatà C; Division of Translational Cancer Research, German Cancer Research Center and German Cancer Consortium, Heidelberg, Germany.; Chair of Translational Cancer Research and Institute of Experimental Cancer Therapy, University Hospital Rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany.; Center for Translational Cancer Research (TranslaTUM), School of Medicine, Technical University of Munich, Munich, Germany., Fink D; Institute of Innate Immunity, Department of Systems Immunology and Proteomics, Medical Faculty, University of Bonn, Bonn, Germany., Sinha A; Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany., Cheng J; Experimental Systems Immunology, Max Planck Institute of Biochemistry, Martinsried, Germany., Ebner S; Institute of Innate Immunity, Department of Systems Immunology and Proteomics, Medical Faculty, University of Bonn, Bonn, Germany., Landgraf P; Institute for Pharmacology and Toxicology, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany., Dieterich DC; Institute for Pharmacology and Toxicology, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany.; Center for Behavioral Brain Sciences, Magdeburg, Germany., Daub H; NEOsphere Biotechnologies GmbH, Martinsried, Germany., Saur D; Division of Translational Cancer Research, German Cancer Research Center and German Cancer Consortium, Heidelberg, Germany. dieter.saur@tum.de.; Chair of Translational Cancer Research and Institute of Experimental Cancer Therapy, University Hospital Rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany. dieter.saur@tum.de.; Center for Translational Cancer Research (TranslaTUM), School of Medicine, Technical University of Munich, Munich, Germany. dieter.saur@tum.de., Meissner F; Experimental Systems Immunology, Max Planck Institute of Biochemistry, Martinsried, Germany. felix.meissner@uni-bonn.de.; Institute of Innate Immunity, Department of Systems Immunology and Proteomics, Medical Faculty, University of Bonn, Bonn, Germany. felix.meissner@uni-bonn.de.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 May 08; Vol. 14 (1), pp. 2642. Date of Electronic Publication: 2023 May 08.
DOI: 10.1038/s41467-023-38171-8
Abstrakt: Cell-selective proteomics is a powerful emerging concept to study heterocellular processes in tissues. However, its high potential to identify non-cell-autonomous disease mechanisms and biomarkers has been hindered by low proteome coverage. Here, we address this limitation and devise a comprehensive azidonorleucine labeling, click chemistry enrichment, and mass spectrometry-based proteomics and secretomics strategy to dissect aberrant signals in pancreatic ductal adenocarcinoma (PDAC). Our in-depth co-culture and in vivo analyses cover more than 10,000 cancer cell-derived proteins and reveal systematic differences between molecular PDAC subtypes. Secreted proteins, such as chemokines and EMT-promoting matrisome proteins, associated with distinct macrophage polarization and tumor stromal composition, differentiate classical and mesenchymal PDAC. Intriguingly, more than 1,600 cancer cell-derived proteins including cytokines and pre-metastatic niche formation-associated factors in mouse serum reflect tumor activity in circulation. Our findings highlight how cell-selective proteomics can accelerate the discovery of diagnostic markers and therapeutic targets in cancer.
(© 2023. The Author(s).)
Databáze: MEDLINE
Externí odkaz: