Dataset Information

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

ABSTRACT: Cell-selective proteomics is emerging as a powerful concept for studying heterocellular processes. However, its potential to dissect intercellular signaling has not been exploited, despite its promise to identify non-cell autonomous disease mechanisms or biomarkers. Here, we devised an improved azidonorleucine-based protein labeling, enrichment, and mass spectrometry workflow, to achieve comprehensive proteome coverage of up to >10,100 cell-selective proteins. We provide proof-of-concept for in depth cell-selective secretomics by dissecting bidirectional intercellular signaling between co-cultured primary pancreatic ductal adenocarcinoma (PDAC) cells and macrophages. In vivo, detection of extracellular proteins emerged as a unique strength compared to FACS-based methods. Our analysis reveals systematic differences of cancer cell-derived matrisome proteins between molecular PDAC subtypes in vivo, such as elevated EMT-signal sustaining proteins. Intriguingly, high levels of pre-metastatic niche formation-associated factors in the serum reflected tumor activity in circulation. Our findings highlight how cell-selective proteomics accelerates the discovery of diagnostic markers and new therapeutic targets in cancer.

INSTRUMENT(S): Q Exactive HF-X, Orbitrap Exploris 480, Q Exactive HF

ORGANISM(S): Homo Sapiens (human) Mus Musculus (mouse)

TISSUE(S): Cell Culture, Pancreas, Macrophage

SUBMITTER: Mario Oroshi

LAB HEAD: Felix Meissner

PROVIDER: PXD040084 | Pride | 2023-07-20

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	01_MetSubstituteIncorporation_SupFig1_raw.zip	Other
	01_MetSubstituteIncorporation_SupFig1_results.zip	Other
	02_EnrichmentMethodComparison_Fig1_raw.zip	Other
	02_EnrichmentMethodComparison_Fig1_results.zip	Other
	03_AcquisitionMethodComparison_Fig1_offlineFractionation_raw.zip	Other

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

Swietlik Jonathan J JJ Bärthel Stefanie S Falcomatà Chiara C Fink Diana D Sinha Ankit A Cheng Jingyuan J Ebner Stefan S Landgraf Peter P Dieterich Daniela C DC Daub Henrik H Saur Dieter D Meissner Felix F

Nature communications 20230508 1

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-de ...[more]

PMID: 37156840

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