Tumour exosomal CEMIP protein promotes cancer cell colonization in brain metastasis.
Animals
Brain
/ metabolism
Brain Neoplasms
/ genetics
Cell Line, Tumor
Cell Movement
Cell Proliferation
Chemokine CCL1
/ genetics
Chemokine CXCL1
/ genetics
Cyclooxygenase 2
/ genetics
Endothelial Cells
/ metabolism
Exosomes
/ metabolism
Gene Expression Regulation, Neoplastic
Humans
Hyaluronoglucosaminidase
/ genetics
Mice
Mice, Inbred C57BL
Mice, Nude
Neoplasm Metastasis
Neovascularization, Pathologic
/ genetics
Signal Transduction
Survival Analysis
Tumor Burden
Tumor Microenvironment
/ genetics
Tumor Necrosis Factor-alpha
/ genetics
Xenograft Model Antitumor Assays
Journal
Nature cell biology
ISSN: 1476-4679
Titre abrégé: Nat Cell Biol
Pays: England
ID NLM: 100890575
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
30
05
2019
accepted:
19
09
2019
pubmed:
7
11
2019
medline:
20
2
2020
entrez:
6
11
2019
Statut:
ppublish
Résumé
The 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
Identifiants
pubmed: 31685984
doi: 10.1038/s41556-019-0404-4
pii: 10.1038/s41556-019-0404-4
pmc: PMC7354005
mid: NIHMS1604880
doi:
Substances chimiques
CCL1 protein, human
0
CXCL1 protein, human
0
Chemokine CCL1
0
Chemokine CXCL1
0
Tumor Necrosis Factor-alpha
0
Cyclooxygenase 2
EC 1.14.99.1
PTGS2 protein, human
EC 1.14.99.1
CEMIP protein, human
EC 3.2.1.35
Hyaluronoglucosaminidase
EC 3.2.1.35
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1403-1412Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA169538
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA193461
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA217169
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA232093
Pays : United States
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