PXD046421

PXD046421 is an original dataset announced via ProteomeXchange.

Title	Second-Hand Melanoma Melanosomes Regulate Diversity Among Tumor-Associated Macrophages
Description	Extracellular vesicles (EVs) are a key form of cell-to-cell communication. Here we reveal a new mode of communication involving the large EVs, melanosomes. Unlike small EVsexosomes, which are dissolved in the receiver cell, melanosomes stay intact within them, gain a unique protein signature, and can then be further transferred to another cell, a state we term “second-hand EVs”. We found that melanoma-secreted melanosomes uptaken by and then released from epidermal keratinocytes or dermal fibroblasts can be further engulfed by resident macrophages. The respective consequence for macrophages is polarization into pro-tumor or pro-immune-cell-infiltration phenotypes. Fibroblasts load melanosomes with AKT1, which induces VEGF secretion from macrophages in an mTOR-dependent manner, promoting angiogenesis and metastasis in-vivo. In melanoma patients, macrophages co-localized with AKT1, were correlated with disease aggressiveness, and immunotherapy non-responders were enriched in macrophages containing melanosome markers. Thus, the network of interactions via second-hand EVs helps form the metastatic niche. Since macrophage heterogeneity is pivotal in advancement of cancer, our data suggest an opportunity to halt melanoma progression by blocking the melanosome cues of macrophage diversification.
HostingRepository	PRIDE
AnnounceDate	2023-12-31
AnnouncementXML	Submission_2023-12-31_06:05:27.253.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tamar Ziv
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-10-26 07:52:08	ID requested
⏵ 1	2023-12-31 06:05:27	announced

Dataset with its publication pending

submitter keyword: Melanosomes, macrophages, small EV

Carmit Levy
contact affiliation	Department of Human Genetics and Biochemistry Sackler School of Medicine Tel Aviv University Tel-Aviv, Israel 69978
contact email	carmitlevy@post.tau.ac.il
lab head
Tamar Ziv
contact affiliation	Technion
contact email	tamarz@technion.ac.il
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/2023/12/PXD046421

PRIDE project URI

• PRIDE
  1. PXD046421
     1. Label: PRIDE project
     2. Name: Second-Hand Melanoma Melanosomes Regulate Diversity Among Tumor-Associated Macrophages