Extracellular vesicles from genetically unstable, oncogene-driven cancer cells trigger micronuclei formation in endothelial cells.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
22 05 2020
22 05 2020
Historique:
received:
19
02
2020
accepted:
07
05
2020
entrez:
24
5
2020
pubmed:
24
5
2020
medline:
2
12
2020
Statut:
epublish
Résumé
Oncogenic transformation impacts cancer cell interactions with their stroma, including through formation of abnormal blood vessels. This influence is often attributed to angiogenic growth factors, either soluble, or associated with tumor cell-derived extracellular vesicles (EVs). Here we examine some of the cancer-specific components of EV-mediated tumor-vascular interactions, including the impact of genetic driver mutations and genetic instability. Cancer cells expressing mutant HRAS oncogene exhibit aberrations of chromatin architecture, aneuploidy, cytoplasmic chromatin deposition and formation of micronuclei with a non-random chromosome content. EVs released from such HRAS-driven cells carry genomic DNA, including oncogenic sequences, and transfer this material to endothelial cells while inducing abnormal formation of micronuclei, along with cell migration and proliferation. Micronuclei were also triggered following treatment with EVs derived from glioma cells (and stem cells) expressing EGFRvIII oncogene, and in both endothelial cells and astrocytes. EVs from HRAS and EGFRvIII-driven cancer cells carry 19 common proteins while EVs from indolent control cells exhibit more divergent proteomes. Immortalized endothelial cell lines with disrupted TP53 pathway were refractory to EV-mediated micronuclei induction. We suggest that oncogenic transformation and intercellular trafficking of cancer-derived EVs may contribute to pathological vascular responses in cancer due to intercellular transmission of genomic instability.
Identifiants
pubmed: 32444772
doi: 10.1038/s41598-020-65640-7
pii: 10.1038/s41598-020-65640-7
pmc: PMC7244541
doi:
Substances chimiques
Proteome
0
HRAS protein, human
EC 3.6.5.2
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
8532Subventions
Organisme : CIHR
ID : FDN 143322
Pays : Canada
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