Extracellular vesicles from human liver stem cells inhibit renal cancer stem cell-derived tumor growth in vitro and in vivo.
Administration, Intravenous
Animals
Biological Products
/ administration & dosage
Biological Therapy
/ methods
Cell Fractionation
Extracellular Vesicles
/ metabolism
Gene Expression Regulation, Neoplastic
/ drug effects
Humans
Kidney
/ cytology
Kidney Neoplasms
/ pathology
Liver
/ cytology
Mesenchymal Stem Cells
/ cytology
Mice
MicroRNAs
/ metabolism
Neoplastic Stem Cells
/ drug effects
Nephrectomy
Primary Cell Culture
Tissue Distribution
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
antitumor therapy
exRNA
exosomes
microRNA
renal cell carcinoma
Journal
International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124
Informations de publication
Date de publication:
15 09 2020
15 09 2020
Historique:
received:
19
07
2019
revised:
28
01
2020
accepted:
04
02
2020
pubmed:
18
2
2020
medline:
15
4
2021
entrez:
18
2
2020
Statut:
ppublish
Résumé
Cancer stem cells (CSCs) are considered as responsible for initiation, maintenance and recurrence of solid tumors, thus representing the key for tumor eradication. The antitumor activity of extracellular vesicles (EVs) derived from different stem cell sources has been investigated with conflicting results. In our study, we evaluated, both in vitro and in vivo, the effect of EVs derived from human bone marrow mesenchymal stromal cells (MSCs) and from a population of human liver stem cells (HLSCs) of mesenchymal origin on renal CSCs. In vitro, both EV sources displayed pro-apoptotic, anti-proliferative and anti-invasive effects on renal CSCs, but not on differentiated tumor cells. Pre-treatment of renal CSCs with EVs, before subcutaneous injection in SCID mice, delayed tumor onset. We subsequently investigated the in vivo effect of MSC- and HLSC-EVs systemic administration on progression of CSC-generated renal tumors. Tumor bio-distribution analysis identified intravenous treatment as best route of administration. HLSC-EVs, but not MSC-EVs, significantly impaired subcutaneous tumor growth by reducing tumor vascularization and inducing tumor cell apoptosis. Moreover, intravenous treatment with HLSC-EVs improved metastasis-free survival. In EV treated tumor explants, we observed both the transfer and the induction of miR-145 and of miR-200 family members. In transfected CSCs, the same miRNAs affected cell growth, invasion and survival. In conclusion, our results showed a specific antitumor effect of HLSC-EVs on CSC-derived renal tumors in vivo, possibly ascribed to the transfer and induction of specific antitumor miRNAs. Our study provides further evidence for a possible clinical application of stem cell-EVs in tumor treatment.
Identifiants
pubmed: 32064610
doi: 10.1002/ijc.32925
pmc: PMC7496472
doi:
Substances chimiques
Biological Products
0
MIRN145 microRNA, human
0
MIRN200 microRNA, human
0
MicroRNAs
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1694-1706Informations de copyright
© 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.
Références
Br J Cancer. 2013 Jun 25;108(12):2525-36
pubmed: 23801032
Stem Cells Transl Med. 2018 Mar;7(3):283-294
pubmed: 29431914
Mol Cancer Ther. 2018 Jul;17(7):1355-1364
pubmed: 29967214
PLoS One. 2013 Dec 31;8(12):e84256
pubmed: 24391924
PLoS One. 2014 May 05;9(5):e96836
pubmed: 24797571
EMBO Mol Med. 2016 Jul 01;8(7):702-11
pubmed: 27189167
Sci Signal. 2014 Jul 01;7(332):ra63
pubmed: 24985346
Cell Cycle. 2015 Aug 3;14(15):2473-83
pubmed: 26091251
Tissue Eng Part A. 2017 Nov;23(21-22):1262-1273
pubmed: 28471327
Oncotarget. 2018 Nov 16;9(90):36151-36165
pubmed: 30546834
Am J Physiol Cell Physiol. 2014 Apr 1;306(7):C621-33
pubmed: 24452373
Stem Cells Dev. 2013 Mar 1;22(5):758-71
pubmed: 23034046
Oncotarget. 2017 Aug 24;8(59):99624-99636
pubmed: 29245929
Sci Rep. 2019 Mar 14;9(1):4468
pubmed: 30872726
Oncotarget. 2018 Apr 27;9(32):22680-22692
pubmed: 29854307
Mol Med Rep. 2014 Jul;10(1):393-8
pubmed: 24737449
Exp Mol Med. 2019 Mar 15;51(3):1-12
pubmed: 30872574
Histopathology. 2019 Jan;74(1):18-30
pubmed: 30565307
Int J Mol Med. 2014 May;33(5):1055-63
pubmed: 24573178
Neoplasia. 2013 Feb;15(2):218-30
pubmed: 23441135
J Clin Invest. 2013 Apr;123(4):1542-55
pubmed: 23454749
Mol Med Rep. 2016 Oct;14(4):3452-8
pubmed: 27513187
J Cell Mol Med. 2014 Oct;18(10):1913-26
pubmed: 25124875
PLoS One. 2017 Jan 9;12(1):e0169899
pubmed: 28068409
Int J Cancer. 2019 Jan 15;144(2):322-333
pubmed: 30110127
J Cell Biol. 2013 Feb 18;200(4):373-83
pubmed: 23420871
FASEB J. 2008 Oct;22(10):3696-705
pubmed: 18614581
Cell Death Dis. 2018 Feb 13;9(2):218
pubmed: 29440630
Mol Cancer Res. 2013 Feb;11(2):182-93
pubmed: 23233482
Cancer Lett. 2012 Feb 1;315(1):28-37
pubmed: 22055459
Stem Cells. 2006 Dec;24(12):2840-50
pubmed: 16945998
Genes Chromosomes Cancer. 2013 Feb;52(2):165-73
pubmed: 23074016
Pharmacol Res. 2016 Sep;111:487-500
pubmed: 27394168
Am J Cancer Res. 2011;1(1):98-110
pubmed: 21969178
Biochem Biophys Res Commun. 2018 May 23;499(4):1004-1010
pubmed: 29627574
J Extracell Vesicles. 2013 Jan 10;2:
pubmed: 24009896
Cancer Res. 2011 Aug 1;71(15):5346-56
pubmed: 21670082
J Cancer Res Clin Oncol. 2014 Mar;140(3):387-97
pubmed: 24384875
Tissue Eng Part C Methods. 2010 Feb;16(1):123-32
pubmed: 19397473
Stem Cell Res Ther. 2017 Jul 27;8(1):176
pubmed: 28750687
PLoS One. 2013 Apr 12;8(4):e61366
pubmed: 23593475
Stem Cells. 2012 Sep;30(9):1985-98
pubmed: 22736596
Int J Oncol. 2015 Mar;46(3):1031-8
pubmed: 25544346
Int J Nanomedicine. 2019 Apr 23;14:2847-2859
pubmed: 31114198
Front Oncol. 2014 Mar 17;4:49
pubmed: 24672771
Cancer Lett. 2013 Sep 10;338(1):141-6
pubmed: 22587951
Eur Urol. 2015 Mar;67(3):519-30
pubmed: 25449206
Int J Cancer. 2011 Nov 15;129(10):2315-27
pubmed: 21792897
Int J Oncol. 2019 May;54(5):1843-1852
pubmed: 30864702
Oncotarget. 2019 Mar 8;10(20):1872-1873
pubmed: 30956770