PXD023165

PXD023165 is an original dataset announced via ProteomeXchange.

Title	CD9, a key mediator of pancreatic cancer cell aggressiveness driven by CAFs-derived extracellular vesicles
Description	While of growing interest in pancreatic cancer (PC) field, the stromal-tumor cells crosstalk lags behind in terms of biomarkers and therapeutic options improving the clinical armamentarium. Knowledge on cellular communications was drastically enhanced following the discovery of extracellular vesicles (EVs), a powerful process of intercellular exchanges. We previously described a new stromal-tumor cell crosstalk mediated by Cancer-Associated Fibroblasts (CAFs)-derived ANXA6+-EVs, supporting pancreatic cancer cell aggressiveness in hostile areas of PC. In this study, using mass spectrometry analyses to investigate CAFs-derived EVs' cargo, we report that CD9 is a key member of the ANXA6/LRP1/TSP1 complex present in PC-associated CAFs-derived ANXA6+-EVs. We determined that CD9 is expressed by PC-associated CAFs in vivo as well as in vitro following physiopathologic culture conditions. Targeting CD9 impaired CAFs-derived ANXA6+-EVs uptake by pancreatic cancer cells, which consequently decreases their migratory abilities. Signaling pathway arrays highlighted p38/MAPK as activated in pancreatic cancer cells following CAFs-derived ANXA6+/CD9+-EVs uptake. The use of CD9 blocking antibody, p38 siRNA or chemical inhibitors impaired pancreatic cancer cells abilities following incubation with CAFs-derived ANXA6+/CD9+-EVs. Finally, we revealed CD9 expression as an independent poor-prognosis marker in human PC samples. Collectively our data highlight the key role of CD9 in CAFs-derived ANXA6+-EVs internalization by pancreatic cancer cells and the consequent, and mandatory, activation of p38/MAPK pathway to foster their migratory abilities. Measuring the oncogenic CAFs-derived ANXA6+/CD9+-EVs then limiting their action on pancreatic cancer cells abilities might be a promising option for PC stratification and treatment.
HostingRepository	PRIDE
AnnounceDate	2022-08-21
AnnouncementXML	Submission_2022-08-21_12:53:19.382.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	AUDEBERT Stephane
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2020-12-16 01:31:19	ID requested
⏵ 1	2022-08-21 12:53:20	announced

Nigri J, Leca J, Tubiana SS, Finetti P, Guillaumond F, Martinez S, Lac S, Iovanna JL, Audebert S, Camoin L, Vasseur S, Bertucci F, Tomasini R, CD9 mediates the uptake of extracellular vesicles from cancer-associated fibroblasts that promote pancreatic cancer cell aggressiveness. Sci Signal, 15(745):eabg8191(2022) [pubmed]

submitter keyword: Extra-cellular Vesicles (EVs), Stromal compartment, Pancreatic cancer (PC), LC-MSMS, Cancer-Associated Fibroblasts (CAFs), CD9, Migration, p38/MAPK pathway

Tomasini Richard
contact affiliation	1INSERM, U1068, Cancer Research Center of Marseille, Institut Paoli-Calmettes, CNRS, UMR7258, and University Aix-Marseille, Marseille, France
contact email	richard.tomasini@inserm.fr
lab head
AUDEBERT Stephane
contact affiliation	Pharmacology department
contact email	stephane.audebert@inserm.fr
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/08/PXD023165

PRIDE project URI

• PRIDE
  1. PXD023165
     1. Label: PRIDE project
     2. Name: CD9, a key mediator of pancreatic cancer cell aggressiveness driven by CAFs-derived extracellular vesicles