PXD047563-1

PXD047563 is an original dataset announced via ProteomeXchange.

Dataset Summary

Title	Extracellular vesicles from pancreatic cancer cells activate mast cells which in turn promote tumor cell proliferation and establish a tumor-supportive microenvironment
Description	Background and aim: Recent studies reveal a critical role of tumor cell-released extracellular vesicles (EVs) in pancreatic cancer progression. Driver genes directing EV function, the EV-recipient cells, as well as their cellular response to EV uptake remain, however, to be identified. To address this, we investigated the role of the EV biogenesis regulator Bcl-2-associated-anthanogene6 (BAG6)for cancer progression. Methods: We used a cre recombinase/loxP-based reporter system in combination with single-cell RNA sequencing to monitor in vivo EV uptake and tumor microenvironment (TME) changes in preclinical mouse models for pancreatic ductal adenocarcinoma (PDAC) in a Bag6 pro- or deficient background. In vivo data were validated using mouse and human organoids, as well aspatient samples. Results: Bag6-deficient subcutaneous and orthotopic PDAC tumors showed accelerated tumor growth dependent on EV release. Mechanistically, this was attributed to mast cell (MC) activation via EV-associate IL33. Activated MCs promoted tumor cell proliferation and altered the composition of the TME affecting fibroblast polarization and immune cell infiltration. Tumor cell proliferation and TME remodeling were mediated via the MC secretome containing high levels of PDGF and CD73. In patients, BAG6 gene expression and protein serum level correlated with survival and low MC infiltration indicating clinical relevance. Conclusion: The study revealed a tumor-suppressing activity of BAG6 in PDAC, unknown up to now. Bag6-deficiency allowed the release of Evs-associated IL33 which shaped the composition of the TME via MC activation causing aggressive tumor growth. MC depletion using Imatinib diminished tumor growth providing a scientific rationale for the evaluation of Imatinib treatment of patients stratified for low BAG6 expression and high MC infiltration.
HostingRepository	MassIVE
AnnounceDate	2025-06-23
AnnouncementXML	Submission_2025-06-23_12:42:56.114.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Witold Szymanski
SpeciesList	scientific name: Mus musculus; common name: house mouse; NCBI TaxID: 10090;
ModificationList	Deamidated:18O(1); iodoacetamide - site C; Acetyl
Instrument	timsTOF Pro

Dataset History

Revision	Datetime	Status	ChangeLog Entry
0	2023-12-06 01:20:22	ID requested
⏵ 1	2025-06-23 12:42:56	announced

Publication List

Alashkar Alhamwe B, Ponath V, Alhamdan F, D, ö, rsam B, Landwehr C, Linder M, Pauck K, Miethe S, Garn H, Finkernagel F, Brichkina A, Lauth M, Tiwari DK, Buchholz M, Bachurski D, Elmsh, ä, user S, Nist A, Stiewe T, Pogge von Strandmann L, Szyma, ń, ski W, Beutgen V, Graumann J, Teply-Szymanski J, Keber C, Denkert C, Jacob R, Preu, ß, er C, Pogge von Strandmann E, BAG6 restricts pancreatic cancer progression by suppressing the release of IL33-presenting extracellular vesicles and the activation of mast cells. Cell Mol Immunol, 21(8):918-931(2024) [pubmed]

Alashkar Alhamwe B, Ponath V, Alhamdan F, D, ö, rsam B, Landwehr C, Linder M, Pauck K, Miethe S, Garn H, Finkernagel F, Brichkina A, Lauth M, Tiwari DK, Buchholz M, Bachurski D, Elmsh, ä, user S, Nist A, Stiewe T, Pogge von Strandmann L, Szyma, ń, ski W, Beutgen V, Graumann J, Teply-Szymanski J, Keber C, Denkert C, Jacob R, Preu, ß, er C, Pogge von Strandmann E, BAG6 restricts pancreatic cancer progression by suppressing the release of IL33-presenting extracellular vesicles and the activation of mast cells. Cell Mol Immunol, 21(8):918-931(2024) [pubmed]

Keyword List

submitter keyword: extracellular vesicles, mouse, pancreatic cancer, TimsTof Pro, DDA, Bag6

submitter keyword: extracellular vesicles, mouse, pancreatic cancer, TimsTof Pro, DDA, Bag6

Contact List

Elke Pogge von Strandmann
contact affiliation	Institute for Tumor Immunology, Philipps-University Marburg
contact email	poggevon@staff.uni-marburg.de
lab head
Witold Szymanski
contact affiliation	Philipps-University Marburg Biochemical/Pharmacological Center Department of Medicine
contact email	witold.szymanski@uni-marburg.de
dataset submitter

Full Dataset Link List

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MassIVE dataset URI

Dataset FTP location
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