PXD028597

PXD028597 is an original dataset announced via ProteomeXchange.

Title	A multi-omics approach identifies pancreatic cancer cell extracellular vesicles as mediators of the unfolded protein response in normal pancreatic epithelial cells.
Description	Although cancer derived extracellular vesicles (cEVs) are thought to play a pivotal role in promoting cancer progression events, their precise effect on neighboring normal cells is unknown. In this study, we investigated the impact of pancreatic cancer ductal adenocarcinoma (PDAC) derived EVs on recipient non-tumorigenic pancreatic normal epithelial cells upon internalization. We show that PDAC cEVs increase the proliferation and invasive capability of recipient normal cells. We further demonstrate that cEVs induce endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) in recipient normal pancreatic epithelial cells within 24 hours. Subsequently, leveraging a layered multi-omics approach, we analyzed EV cargo from a panel of 6 PDAC and 2 normal pancreas cell lines, using multiple EV isolation methods. We found that cEVs were enriched for an array of biomolecules which can induce or regulate ER stress and the UPR, including palmitic acid, sphingomyelins, metabolic regulators of tRNA charging and proteins responsible for protein trafficking and degradation. We further show that palmitic acid, at doses relevant to those found in cEVs, is sufficient to induce ER stress in normal pancreas cells. These results suggest that cEV cargo packaging may be designed to disseminate proliferative and invasive characteristics upon internalization by distant recipient normal cells, hitherto unreported. This study is among the first to highlight a major role for PDAC cEVs to induce stress in recipient normal pancreas cells, that may modulate a systemic response leading to altered phenotypes. For the first time, our study implicates cEV transported palmitic acid as a potential driver in this process. These findings reveal new paths of investigation toward understanding the role of lipids packaged as cEV cargo providing advantage to proliferating tumor cells in promoting cell transformation in the surrounding microenvironment.
HostingRepository	PRIDE
AnnounceDate	2022-08-12
AnnouncementXML	Submission_2022-08-11_22:44:43.495.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD028597
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Amrita Cheema
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-09-16 23:27:47	ID requested
⏵ 1	2022-08-11 22:44:44	announced

Hinzman CP, Singh B, Bansal S, Li Y, Iliuk A, Girgis M, Herremans KM, Trevino JG, Singh VK, Banerjee PP, Cheema AK, A multi-omics approach identifies pancreatic cancer cell extracellular vesicles as mediators of the unfolded protein response in normal pancreatic epithelial cells. J Extracell Vesicles, 11(6):e12232(2022) [pubmed]

submitter keyword: Human, Pancreas, Cancer, Extracellular Vesicles

Amrita K Cheema
contact affiliation	Professor of Oncology and Biochemistry Associate Director: Center for Metabolomic Studies. Georgetown University Medical Center Washington, DC, USA 20007
contact email	Amrita.Cheema@georgetown.edu
lab head
Amrita Cheema
contact affiliation	Georgetown University Medical Center
contact email	Amrita.Cheema@georgetown.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD028597
     1. Label: PRIDE project
     2. Name: A multi-omics approach identifies pancreatic cancer cell extracellular vesicles as mediators of the unfolded protein response in normal pancreatic epithelial cells.