PXD015210

PXD015210 is an original dataset announced via ProteomeXchange.

Title	Tumour exosomal CEMIP protein promotes cancer cell colonization in brain metastasis
Description	Development of effective therapies against brain metastasis is currently hindered by limitations in our understanding of the molecular mechanisms driving it. Here we define the contributions of tumour-secreted exosomes to brain metastatic colonization and demonstrate that pre-conditioning the brain microenvironment with exosomes from brain metastatic cells enhances cancer cell outgrowth. Proteomic analysis identified cell migration-inducing and hyaluronan-binding protein (CEMIP) as elevated in exosomes from brain metastatic, but not lung or bone metastatic cells. CEMIP depletion in tumour cells impaired brain metastasis, disrupting invasion and tumour cell association with the brain vasculature, phenotypes rescued by pre-conditioning the brain microenvironment with CEMIP+ exosomes. Moreover, uptake of CEMIP+ exosomes by brain endothelial and microglial cells induced endothelial cell branching and inflammation in the perivascular niche by upregulating Ptgs2, Tnf, and Ccl/Cxcl 86 cytokines, known to promote brain vascular remodeling and metastasis. CEMIP was elevated in tumour tissues and exosomes from patients with brain metastasis and predicted brain metastasis progression and patient survival. Collectively, our findings suggest that targeting of exosomal CEMIP could constitute a future avenue for the prevention and treatment of brain metastasis.
HostingRepository	PRIDE
AnnounceDate	2022-02-15
AnnouncementXML	Submission_2022-02-15_09:24:03.123.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	henrik molina
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-08-29 03:37:22	ID requested
⏵ 1	2022-02-15 09:24:03	announced

Rodrigues G, Hoshino A, Kenific CM, Matei IR, Steiner L, Freitas D, Kim HS, Oxley PR, Scandariato I, Casanova-Salas I, Dai J, Badwe CR, Gril B, Te, š, i, ć, Mark M, Dill BD, Molina H, Zhang H, Benito-Martin A, Bojmar L, Ararso Y, Offer K, LaPlant Q, Buehring W, Wang H, Jiang X, Lu TM, Liu Y, Sabari JK, Shin SJ, Narula N, Ginter PS, Rajasekhar VK, Healey JH, Meylan E, Costa-Silva B, Wang SE, Rafii S, Altorki NK, Rudin CM, Jones DR, Steeg PS, Peinado H, Ghajar CM, Bromberg J, de Sousa M, Pisapia D, Lyden D, Tumour exosomal CEMIP protein promotes cancer cell colonization in brain metastasis. Nat Cell Biol, 21(11):1403-1412(2019) [pubmed]

submitter keyword: Tumour exosomal CEMI brain metastasis

Lyden, David
contact affiliation	Weill Cornell Medicine
contact email	dcl2001@med.cornell.edu
lab head
henrik molina
contact affiliation	THE ROCKEFELLER UNIVERSITY
contact email	henrik.molina@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD015210
     1. Label: PRIDE project
     2. Name: Tumour exosomal CEMIP protein promotes cancer cell colonization in brain metastasis