Small extracellular vesicles ameliorate peripheral neuropathy and enhance chemotherapy of oxaliplatin on ovarian cancer.
Animals
Antineoplastic Agents
/ adverse effects
Axons
/ drug effects
Cell Line, Tumor
Extracellular Vesicles
/ metabolism
Female
Humans
Mice, Inbred C57BL
Mice, Nude
MicroRNAs
/ metabolism
Neoplasm Proteins
/ metabolism
Neoplasm Transplantation
Nerve Fibers
/ metabolism
Nerve Fibers, Myelinated
/ metabolism
Ovarian Neoplasms
/ drug therapy
Oxaliplatin
/ administration & dosage
Peripheral Nervous System Diseases
/ chemically induced
Chemotherapy‐induced peripheral neuropathy
microRNAs
ovarian cancer
small extracellular vesicles
Journal
Journal of extracellular vesicles
ISSN: 2001-3078
Titre abrégé: J Extracell Vesicles
Pays: United States
ID NLM: 101610479
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
05
08
2020
revised:
07
01
2021
accepted:
13
02
2021
entrez:
17
3
2021
pubmed:
18
3
2021
medline:
18
3
2021
Statut:
ppublish
Résumé
There are no effective treatments for chemotherapy induced peripheral neuropathy (CIPN). Small extracellular vesicles (sEVs) facilitate intercellular communication and mediate nerve function and tumour progression. We found that the treatment of mice bearing ovarian tumour with sEVs derived from cerebral endothelial cells (CEC-sEVs) in combination with a chemo-drug, oxaliplatin, robustly reduced oxaliplatin-induced CIPN by decreasing oxaliplatin-damaged myelination and nerve fibres of the sciatic nerve and significantly amplified chemotherapy of oxaliplatin by reducing tumour size. The combination therapy substantially increased a set of sEV cargo-enriched miRNAs, but significantly reduced oxaliplatin-increased proteins in the sciatic nerve and tumour tissues. Bioinformatics analysis revealed the altered miRNAs and proteins formed two distinct networks that regulate neuropathy and tumour growth, respectively. Intravenously administered CEC-sEVs were internalized by axons of the sciatic nerve and cancer cells. Reduction of CEC-sEV cargo miRNAs abolished the effects of CEC-sEVs on oxaliplatin-inhibited axonal growth and on amplification of the anti-cancer effect in ovarian cancer cells, suggesting that alterations in the networks of miRNAs and proteins in recipient cells contribute to the therapeutic effect of CEC-sEVs on CIPN. Together, the present study demonstrates that CEC-sEVs suppressed CIPN and enhanced chemotherapy of oxaliplatin in the mouse bearing ovarian tumour.
Identifiants
pubmed: 33728031
doi: 10.1002/jev2.12073
pii: JEV212073
pmc: PMC7931803
doi:
Substances chimiques
Antineoplastic Agents
0
MicroRNAs
0
Neoplasm Proteins
0
Oxaliplatin
04ZR38536J
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Pagination
e12073Subventions
Organisme : NCI NIH HHS
ID : R01 CA219829
Pays : United States
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2021 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.
Déclaration de conflit d'intérêts
No
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