Demeclocycline Reduces the Growth of Human Brain Tumor-Initiating Cells: Direct Activity and Through Monocytes.
glioma
innate immunity
macrophages
microglia
monocytes
stem cells
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2020
2020
Historique:
received:
28
10
2019
accepted:
03
02
2020
entrez:
11
3
2020
pubmed:
11
3
2020
medline:
9
3
2021
Statut:
epublish
Résumé
Myeloid cells that infiltrate into brain tumors are deactivated or exploited by the tumor cells. We previously demonstrated that compromised microglia, monocytes, and macrophages in malignant gliomas could be reactivated by amphotericin-B to contain the growth of brain tumorinitiating cells (BTICs). We identified meclocycline as another activator of microglia, so we sought to test whether its better-tolerated derivative, demeclocycline, also stimulates monocytes to restrict BTIC growth. Monocytes were selected for study as they would be exposed to demeclocycline in the circulation prior to entry into brain tumors to become macrophages. We found that demeclocycline increased the activity of monocytes in culture, as determined by tumor necrosis factor-α production and chemotactic capacity. The conditioned medium of demeclocycline-stimulated monocytes attenuated the growth of BTICs generated from human glioblastoma resections, as evaluated using neurosphere and alamarBlue assays, and cell counts. Demeclocycline also had direct effects in reducing BTIC growth. A global gene expression screen identified several genes, such as DNA damage inducible transcript 4, frizzled class receptor 5 and reactive oxygen species modulator 1, as potential regulators of demeclocycline-mediated BTIC growth reduction. Amongst several tetracycline derivatives, only demeclocycline directly reduced BTIC growth. In summary, we have identified demeclocycline as a novel inhibitor of the growth of BTICs, through direct effect and through indirect stimulation of monocytes. Demeclocycline is a candidate to reactivate compromised immune cells to improve the prognosis of patients with gliomas.
Identifiants
pubmed: 32153581
doi: 10.3389/fimmu.2020.00272
pmc: PMC7047330
doi:
Substances chimiques
Antineoplastic Agents
0
Demeclocycline
5R5W9ICI6O
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
272Subventions
Organisme : CIHR
Pays : Canada
Informations de copyright
Copyright © 2020 Sarkar, Li, Mirzaei, Rawji, Poon, Wang, Kumar, Bose and Yong.
Références
Nature. 2012 Aug 23;488(7412):522-6
pubmed: 22854781
Oncotarget. 2019 May 3;10(33):3129-3143
pubmed: 31139325
J Neurosci. 2015 Jan 21;35(3):1136-48
pubmed: 25609628
J Neurooncol. 2011 Nov;105(2):165-71
pubmed: 21503828
Biol Open. 2019 Sep 12;8(9):
pubmed: 31511246
Nat Rev Cancer. 2006 Jan;6(1):24-37
pubmed: 16397525
Front Biosci (Landmark Ed). 2015 Jun 01;20:1104-15
pubmed: 25961548
Cancer Res. 2017 Jun 15;77(12):3231-3243
pubmed: 28416488
Antimicrob Agents Chemother. 2004 Mar;48(3):985-91
pubmed: 14982793
Oncoimmunology. 2018 Aug 6;7(10):e1478647
pubmed: 30288344
Nature. 2006 Dec 7;444(7120):756-60
pubmed: 17051156
Cancer Res. 2014 Dec 15;74(24):7285-7297
pubmed: 25326491
Mayo Clin Proc. 2019 Jul;94(7):1278-1286
pubmed: 31230743
J Immunol. 2012 Jul 1;189(1):444-53
pubmed: 22664874
Methods Mol Biol. 2020;2058:179-190
pubmed: 31486038
Stem Cells. 2010 Jan;28(1):17-28
pubmed: 19921751
J Neurosurg. 2002 Feb;96(2):294-301
pubmed: 11838804
Neuro Oncol. 2010 Nov;12(11):1113-25
pubmed: 20667896
J Neurooncol. 2015 Jan;121(1):73-81
pubmed: 25193023
Nat Immunol. 2019 Sep;20(9):1100-1109
pubmed: 31358997
Cancers (Basel). 2014 Aug 13;6(3):1670-90
pubmed: 25125485
Front Immunol. 2018 Dec 21;9:2924
pubmed: 30619286
Cell Death Differ. 2006 Jul;13(7):1238-41
pubmed: 16456578
Oncotarget. 2014 Dec 30;5(24):12593-606
pubmed: 25333259
Eur J Endocrinol. 2010 Jun;162 Suppl 1:S13-8
pubmed: 20164215
Glia. 2011 Aug;59(8):1169-80
pubmed: 21446047
J Neurosurg. 2009 Mar;110(3):572-82
pubmed: 19199469
Cancer Cell. 2017 Jul 10;32(1):42-56.e6
pubmed: 28697342
Nat Cell Biol. 2015 Feb;17(2):170-82
pubmed: 25580734
Neuro Oncol. 2006 Jul;8(3):261-79
pubmed: 16775224
J Exp Clin Cancer Res. 2018 Jul 25;37(1):168
pubmed: 30041669
Neuro Oncol. 2012 Jan;14(1):64-78
pubmed: 22015597
Clin Cancer Res. 2019 Jul 15;25(14):4202-4210
pubmed: 30804019
Glia. 2011 Mar;59(3):472-85
pubmed: 21264953
Br J Cancer. 2019 Mar;120(5):481-487
pubmed: 30745581
Biochim Biophys Acta. 2009 Nov;1793(11):1656-68
pubmed: 19748528
Mol Cancer. 2011 Dec 23;10:152
pubmed: 22195643
Neuro Oncol. 2015 Aug;17(8):1095-105
pubmed: 25646025
Nature. 2004 Nov 18;432(7015):396-401
pubmed: 15549107
Lab Invest. 2016 Feb;96(2):137-50
pubmed: 26641068
Neurosurgery. 2007 Feb;60(2):372-80; discussion 381
pubmed: 17290189
Stem Cell Reports. 2015 Jul 14;5(1):1-9
pubmed: 26095605
Pharmaceuticals (Basel). 2013 Nov 25;6(12):1475-506
pubmed: 24287492
Orv Hetil. 1999 Dec 19;140(51):2873-5
pubmed: 10647278
Proc Natl Acad Sci U S A. 2019 Sep 17;116(38):19098-19108
pubmed: 31471491
Neuro Oncol. 2013 Jul;15(7):904-20
pubmed: 23585629
Rev Iberoam Micol. 2009 Dec 31;26(4):223-7
pubmed: 19836985
Front Oncol. 2015 Jan 29;5:5
pubmed: 25688333
Nat Med. 2010 Aug;16(8):861-2
pubmed: 20689550
Front Pharmacol. 2019 Jun 05;10:506
pubmed: 31231208
CNS Neurol Disord Drug Targets. 2013 Sep;12(6):741-9
pubmed: 24047520
Stem Cells. 2009 Aug;27(8):1722-33
pubmed: 19544433
Mol Cancer Res. 2009 Mar;7(3):383-92
pubmed: 19276180
Nature. 2002 Dec 19-26;420(6917):860-7
pubmed: 12490959
Acta Neuropathol. 2002 Feb;103(2):171-8
pubmed: 11810184
Neuro Oncol. 2015 Feb;17(2):200-10
pubmed: 25452390
Cancer Cell. 2017 Aug 14;32(2):253-267.e5
pubmed: 28810147
Int J Radiat Oncol Biol Phys. 2007 Jan 1;67(1):1-5
pubmed: 17084552
Oxid Med Cell Longev. 2019 Aug 5;2019:9719730
pubmed: 31467641
Nat Neurosci. 2014 Jan;17(1):46-55
pubmed: 24316889
Glia. 2012 Mar;60(3):502-14
pubmed: 22379614
Glia. 2019 Dec;67(12):2424-2439
pubmed: 31400163
N Engl J Med. 1978 Jan 26;298(4):173-7
pubmed: 413037
Brain. 2017 Jun 1;140(6):1548-1560
pubmed: 28334886
N Engl J Med. 2005 Mar 10;352(10):987-96
pubmed: 15758009
Phys Med Biol. 2015 Apr 7;60(7):3003-11
pubmed: 25790138