PXD041164

PXD041164 is an original dataset announced via ProteomeXchange.

Title	Cancer cell-derived ADAM15 dictates macrophage infiltration in colorectal tumors
Description	Tumor progression and response to treatment is highly affected by interactions between cancer cells and the tumor microenvironment (TME). Many of the soluble factors and signaling receptors involved in this crosstalk are shed by a disintegrin and metalloproteinases (ADAMs). Upregulation of ADAM15 has been linked to worse survival in cancer patients and a tumor-promoting function both in vitro and in murine cancer models. Although ADAM15 has been involved in cell-cell and cell-extracellular matrix interactions, its role in the crosstalk between cancer cells and the TME in vivo remains unexplored. Therefore, we aimed to understand how ADAM15 regulates the cell composition of the TME and how it affects tumor progression. Here, we showed an upregulation of ADAM15 in tumor tissues from rectal cancer patients. Subcutaneous injection of wildtype and ADAM15-knockout CT26 colon cancer cells in syngeneic mice confirmed the pro-tumorigenic role of ADAM15. Profiling of tumors revealed higher immune cell infiltration and cancer cell apoptosis in the ADAM15-deficient tumors. Specifically, loss of ADAM15 led to a reduced number of granulocytes and higher infiltration of antigen-presenting cells, including dendritic cells and macrophages, as well as more T cells. Using in vitro assays, we confirmed the regulatory effect of ADAM15 on macrophage migration and identified ADAM15-derived CYR61 as a potential molecular mediator of this effect. Together, our data suggest that targeting ADAM15 could increase the infiltration of immune cells in colorectal tumors and thereby turn cold tumors hot, resulting in a potentially improved response to combined immunotherapy.
HostingRepository	PRIDE
AnnounceDate	2023-07-24
AnnouncementXML	Submission_2023-07-24_08:07:24.240.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	KrzysztofPiotrowski
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	2-pyrrolidone-5-carboxylic acid; TMT6plex-126 reporter+balance reagent acylated residue; acetylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-03-28 06:15:21	ID requested
⏵ 1	2023-07-24 08:07:24	announced

Dataset with its publication pending

submitter keyword: LC-MSMS, CYR61,Mouse, TMT, CT26, ADAM15

MarieKveiborg
contact affiliation	Biotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen
contact email	marie.kveiborg@bric.ku.dk
lab head
KrzysztofPiotrowski
contact affiliation	University of Copenhagen (Biotech Research and Innovation Centre)
contact email	krzysztof.piotrowski@bric.ku.dk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD041164
     1. Label: PRIDE project
     2. Name: Cancer cell-derived ADAM15 dictates macrophage infiltration in colorectal tumors