Extracellular vesicles from senescent hepatic stellate cells promote cell viability of hepatoma cells through increasing EGF secretion from differentiated THP-1 cells.
epidermal growth factor
etoposide
extracellular vesicles
hepatic stellate cells
hepatocellular carcinoma
senescence-associated secretory phenotype
Journal
Biomedical reports
ISSN: 2049-9434
Titre abrégé: Biomed Rep
Pays: England
ID NLM: 101613227
Informations de publication
Date de publication:
Apr 2020
Apr 2020
Historique:
received:
08
05
2019
accepted:
17
01
2020
entrez:
20
3
2020
pubmed:
20
3
2020
medline:
20
3
2020
Statut:
ppublish
Résumé
Since the discovery of the senescence-associated secretory phenotype, the role of senescent hepatic stellate cells (HSCs) in hepatocellular carcinoma (HCC) development has gained increasing attention. Similar to cytokines, extracellular vesicles (EVs) are essential for intercellular communication. However, the function of EVs derived from senescent HSCs in HCC progression has not been extensively studied. The aims of the present study were to characterize the EVs derived from senescent HSCs and determine their role in the tumor microenvironment. Cellular senescence was induced in human hepatic stellate cells (HHSteCs) with various concentrations of etoposide. Induction was confirmed using EdU staining and 53BP1 and p21 immunostaining. EVs were isolated by ultracentrifugation and analyzed by nanoparticle tracking analysis. Multiplex immunoassays were used to compare the levels of growth factors secreted from hepatoma cell lines and macrophage cells pretreated with EVs derived from senescent HHSteCs (senescent EVs) with those pretreated with EVs derived from normal cultured HHSteCs (normal EVs). Treatment with 25 µM etoposide for 3 days was the most effective at inducing senescence in HHSteCs. This finding was confirmed by induction of irreversible cell-cycle arrest, upregulation of 53BP1 and p21 expression, and increased SA-β-gal staining. Senescent HHSteCs released increased quantities of EV particles compared with normally cultured HHSteCs. Multiplex analysis revealed that there was no difference between hepatoma cell lines treated with normal EVs and those treated with senescent EVs in growth factor secretion. In contrast, the secretion of epidermal growth factor (EGF) was increased by macrophage cells treated with senescent EVs compared with those treated with normal EVs. Furthermore, senescent EVs did not affect the viability of hepatoma cells but increased the viability of hepatoma cells co-cultured with macrophage cells. In conclusion, the release of EVs from senescent HSCs was higher compared with normal HSCs. Furthermore, senescent EVs promoted HCC development by upregulating EGF secretion from macrophages.
Identifiants
pubmed: 32190304
doi: 10.3892/br.2020.1279
pii: BR-0-0-1279
pmc: PMC7054706
doi:
Types de publication
Journal Article
Langues
eng
Pagination
163-170Informations de copyright
Copyright: © Miyazoe et al.
Références
Best Pract Res Clin Gastroenterol. 2011 Apr;25(2):207-17
pubmed: 21497739
Cell. 2010 Apr 2;141(1):39-51
pubmed: 20371344
Oncogene. 2017 Feb 16;36(7):877-884
pubmed: 27546617
Front Cell Dev Biol. 2018 Feb 20;6:18
pubmed: 29515996
J Cell Biol. 2013 Feb 18;200(4):373-83
pubmed: 23420871
Braz J Med Biol Res. 2013 Oct;46(10):824-30
pubmed: 24141609
Hepatol Res. 2017 Feb;47(2):194-203
pubmed: 27539153
J Clin Invest. 2013 May;123(5):1902-10
pubmed: 23635788
Front Oncol. 2018 Sep 10;8:357
pubmed: 30250825
Nat Med. 2011 Mar;17(3):320-9
pubmed: 21383745
Oncotarget. 2017 Jan 17;8(3):3933-3945
pubmed: 27965469
Nature. 2013 Jul 4;499(7456):97-101
pubmed: 23803760
Carcinogenesis. 2019 May 29;:
pubmed: 31140556
Cell Mol Immunol. 2015 Jan;12(1):1-4
pubmed: 25220733
World J Gastroenterol. 2014 Apr 21;20(15):4128-40
pubmed: 24764651
PLoS One. 2013 Sep 09;8(9):e73054
pubmed: 24039859
Cell Mol Gastroenterol Hepatol. 2015 Nov 1;1(6):646-663.e4
pubmed: 26783552
Hepatology. 2017 May;65(5):1557-1565
pubmed: 28130788
Lancet. 2018 Mar 31;391(10127):1301-1314
pubmed: 29307467
PLoS One. 2013 Jul 11;8(7):e68693
pubmed: 23874726
FEBS J. 2016 Jun;283(12):2219-32
pubmed: 26807763
Physiol Rev. 2008 Jan;88(1):125-72
pubmed: 18195085
Cell. 2008 Aug 22;134(4):657-67
pubmed: 18724938
Hepatology. 2015 Aug;62(2):481-95
pubmed: 25833323
Eur J Cancer Prev. 2018 May;27(3):205-212
pubmed: 29489473
J Extracell Vesicles. 2014 Mar 26;3:
pubmed: 24683445
Lancet. 2009 Feb 14;373(9663):582-92
pubmed: 19217993
Int J Mol Sci. 2017 Feb 14;18(2):
pubmed: 28216578
Oncotarget. 2018 Mar 27;9(23):16400-16417
pubmed: 29662654
Genes Cancer. 2013 Jul;4(7-8):261-72
pubmed: 24167654
Clin Cancer Res. 2017 Jul 1;23(13):3241-3250
pubmed: 28341752
J Virol. 2017 Feb 28;91(6):
pubmed: 28077652
J Neurooncol. 2013 May;113(1):1-11
pubmed: 23456661
Hepatology. 2011 Aug;54(2):707-13
pubmed: 21520207
Nat Commun. 2017 Jun 06;8:15729
pubmed: 28585531
Methods. 2001 Dec;25(4):402-8
pubmed: 11846609
Nat Commun. 2017 Jun 13;8:15691
pubmed: 28608850
Surg Today. 2012 Jan;42(1):1-7
pubmed: 22116397
BMC Gastroenterol. 2015 May 27;15:63
pubmed: 26013123
CA Cancer J Clin. 2015 Mar;65(2):87-108
pubmed: 25651787
Traffic. 2010 May;11(5):675-87
pubmed: 20136776
FASEB J. 2019 Jul;33(7):8530-8542
pubmed: 30970216
Immunity. 2014 Jul 17;41(1):49-61
pubmed: 25035953
Int J Mol Med. 2016 Jul;38(1):3-15
pubmed: 27245147