PXD030077

PXD030077 is an original dataset announced via ProteomeXchange.

Title	A comparative proteomics analysis identified differentially expressed proteins in pancreatic cancer–associated stellate cell small extracellular vesicles
Description	Human pancreatic stellate cells (HPSCs) are an essential stromal component and are the mediators of pancreatic ductal adenocarcinoma (PDAC) progression. Small extracellular vesicles (sEVs) are membrane-enclosed nanoparticles released from stellate cells adjacent to the PDAC. sEVs are believed to play a key role in cell-cell communications and may play a critical role in disease progression. The role of membrane proteins of HPSC sEVs in the PDAC tumor microenvironment is unclear and to date, there has not been a quantitative proteomic comparison of sEVs from normal pancreatic stellate cells (HPaStec) and from PDAC-associated stellate cells (HPSCs). We hypothesized there would be differences in sEVs secretion and membrane protein expression between the 2 conditions that might contribute to PDAC biology. To test these hypotheses, we isolated sEVs using ultracentrifugation followed by characterization by electron microscopy and Nanoparticle Tracking Analysis. HPSCs secreted more sEVs compared to HPaStec, and these sEVs were enriched with exosomal markers, which was confirmed by Western blotting and flow cytometry. HPSC-sEVs also restore the activation of normal stellate cells. Next, we showed that intact membrane-associated proteins may be essential for sufficient uptake of stellate cell sEVs by both normal epithelial and cancer cells. Importantly, we demonstrated that stellate cells in general modulate the cellular proliferations of pancreatic cancer cells although stellate cell sEVs did not change the proliferation of cancer cells. We then compared sEV proteins isolated from HPSCs and HPaStecs cells using liquid chromatography–tandem mass spectrometry. Most of the 1,481 protein groups identified were shared with the exosome database, ExoCarta (http://exocarta.org/; curated by the Mathivanan Lab). Eighty-seven protein groups were differentially expressed (selected by 2-fold difference and adjusted P value ≤ 0.05) between HPSC and HPaStec sEVs. HPSC sEVs contained dramatically more CSE1L, a poor prognostic marker for pancreatic cancer. In conclusion, our findings using mass spectrometry–based proteomics may direct further studies to understand the biology and role of protein composition of HPSC sEVs in PDAC progression or to develop novel strategies based on delivery of exosome cargo to PDAC tumor cells.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:38:50.847.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD030077
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	John Koomen
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-11-30 15:13:00	ID requested
1	2023-03-11 00:01:54	announced
⏵ 2	2023-11-14 08:38:51	announced	2023-11-14: Updated project metadata.

Sarcar B, Fang B, Izumi V, O Nunez Lopez Y, Tassielli A, Pratley R, Jeong D, Permuth JB, Koomen JM, Fleming JB, Stewart PA, A comparative Proteomics Analysis Identified Differentially Expressed Proteins in Pancreatic Cancer-Associated Stellate Cell Small Extracellular Vesicles. Mol Cell Proteomics, 21(12):100438(2022) [pubmed]

10.6019/PXD030077;

submitter keyword: exosomes, human, stellate cells, pancreatic cancer

Paul Stewart
contact affiliation	Moffitt Cancer Center, Tampa, FL, USA
contact email	paul.stewart@moffitt.org
lab head
John Koomen
contact affiliation	Moffitt Cancer Center
contact email	john.koomen@moffitt.org
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD030077
     1. Label: PRIDE project
     2. Name: A comparative proteomics analysis identified differentially expressed proteins in pancreatic cancer–associated stellate cell small extracellular vesicles