Mechanisms of nuclear content loading to exosomes.
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
01
05
2019
accepted:
24
09
2019
entrez:
5
12
2019
pubmed:
5
12
2019
medline:
12
5
2020
Statut:
epublish
Résumé
Exosome cargoes are highly varied and include proteins, small RNAs, and genomic DNA (gDNA). The presence of gDNA suggests that different intracellular compartments contribute to exosome loading, resulting in distinct exosome subpopulations. However, the loading of gDNA and other nuclear contents into exosomes (nExo) remains poorly understood. Here, we identify the relationship between cancer cell micronuclei (MN), which are markers of genomic instability, and nExo formation. Imaging flow cytometry analyses reveal that 10% of exosomes derived from cancer cells and <1% of exosomes derived from blood and ascites from patients with ovarian cancer carry nuclear contents. Treatment with genotoxic drugs resulted in increased MN and nExos both in vitro and in vivo. We observed that multivesicular body precursors and exosomal markers, such as the tetraspanins, directly interact with MN. Collectively, this work provides new insights related to nExos, which have implications for cancer biomarker development.
Identifiants
pubmed: 31799396
doi: 10.1126/sciadv.aax8849
pii: aax8849
pmc: PMC6867874
doi:
Substances chimiques
Biomarkers, Tumor
0
Tetraspanins
0
DNA
9007-49-2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
eaax8849Subventions
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA217685
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA209904
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA096300
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA083639
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA227622
Pays : United States
Organisme : NCATS NIH HHS
ID : UH2 TR000943
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA096297
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA098258
Pays : United States
Informations de copyright
Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).
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