PXD030740

PXD030740 is an original dataset announced via ProteomeXchange.

Title	Epidermal growth factor shedding directs macrophage education in cancer
Description	Macrophages in the tumor microenvironment have a significant impact on tumor progression. Depending on the signaling environment in the tumor, macrophages can either support or constrain tumor growth and metastasis. It is therefore of therapeutic interest to identify the tumor-derived factors that control macrophage education. With this aim, we correlated the expression of ADAM proteases, which are key mediators of cell-cell signaling, to the expression of pro-tumorigenic macrophage markers in human cancer cohorts. We identified ADAM17, a sheddase upregulated in many cancer types, as a protein of interest. Depletion of ADAM17 in cancer cell lines reduced the expression of several pro-tumorigenic markers in neighboring macrophages in vitro as well as in mouse tumor models. Accordingly, ADAM17-/- educated macrophages demonstrated a reduced ability to induce cancer cell invasion. Using quantitative mass spectrometry-based proteomics, we identified HB-EGF, shed by ADAM17 in the cancer cells, as the implicated molecular mediator of macrophage education. Additionally, RNA-seq and ELISA experiments revealed that ADAM17-dependent HB-EGF release induces the expression and secretion of CXCL chemokines in macrophages, which in turn stimulates cancer cell invasion. In conclusion, we provide evidence that ADAM17 mediates a paracrine HB-EGF-chemokine feedback loop, whereby cancer cells hijack macrophages to promote tumor progression.
HostingRepository	PRIDE
AnnounceDate	2022-09-18
AnnouncementXML	Submission_2022-09-18_02:50:58.376.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Krzysztof Piotrowski
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; acetylated residue; 2-pyrrolidone-5-carboxylic acid (Glu); monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-01-05 02:43:22	ID requested
⏵ 1	2022-09-18 02:50:59	announced

Gnosa SP, Puig Blasco L, Piotrowski KB, Freiberg ML, Savickas S, Madsen DH, Auf dem Keller U, Kronqvist P, Kveiborg M, ADAM17-mediated EGFR ligand shedding directs macrophage-promoted cancer cell invasion. JCI Insight, 7(18):(2022) [pubmed]

submitter keyword: Mouse, Conditioned medium, TMT, PRM, LC-MSMS, 4T1, ADAM17, HB-EGF

Marie Kveiborg
contact affiliation	Biotech Research & Innovation Center (BRIC), University of Copenhagen, Denmark
contact email	marie.kveiborg@bric.ku.dk
lab head
Krzysztof Piotrowski
contact affiliation	University of Copenhagen (Biotech Research and Innovation Centre)
contact email	krzysztof.piotrowski@bric.ku.dk
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/2022/09/PXD030740

PRIDE project URI

• PRIDE
  1. PXD030740
     1. Label: PRIDE project
     2. Name: Epidermal growth factor shedding directs macrophage education in cancer