Angiopoietin-2 Combined with Radiochemotherapy Impedes Glioblastoma Recurrence by Acting in an Autocrine and Paracrine Manner: A Preclinical Study.
angiopoietin-2
chemotherapy
glioblastoma
inflammation
microenvironment
radiochemotherapy
radiotherapy
vascularization
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
30 Nov 2020
30 Nov 2020
Historique:
received:
09
10
2020
revised:
06
11
2020
accepted:
25
11
2020
entrez:
3
12
2020
pubmed:
4
12
2020
medline:
4
12
2020
Statut:
epublish
Résumé
(1) We wanted to assess the impact of Ang2 in RCT-induced changes in the environment of glioblastoma. (2) The effect of Ang2 overexpression in tumor cells was studied in the GL261 syngeneic immunocompetent model of GB in response to fractionated RCT. (3) We showed that RCT combined with Ang2 led to tumor clearance for the GL261-Ang2 group by acting on the tumor cells as well as on both vascular and immune compartments. (4) In vitro, Ang2 overexpression in GL261 cells exposed to RCT promoted senescence and induced robust genomic instability, leading to mitotic death. (5) Coculture experiments of GL261-Ang2 cells with RAW 264.7 cells resulted in a significant increase in macrophage migration, which was abrogated by the addition of soluble Tie2 receptor. (6) Together, these preclinical results showed that, combined with RCT, Ang2 acted in an autocrine manner by increasing GB cell senescence and in a paracrine manner by acting on the innate immune system while modulating the vascular tumor compartment. On this preclinical model, we found that an ectopic expression of Ang2 combined with RCT impedes tumor recurrence.
Identifiants
pubmed: 33266255
pii: cancers12123585
doi: 10.3390/cancers12123585
pmc: PMC7760857
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Agence Nationale de la Recherche
ID : ANR-10-EQPX-1401
Organisme : Région Normandie
ID : HABIONOR European project
Organisme : Fédération pour la Recherche sur le Cerveau
ID : Rotary "Espoir en tête"
Organisme : Ministère de l'Enseignement Supérieur et de la Recherche
ID : MESR
Organisme : Centre National de la Recherche Scientifique
ID : CNRS
Organisme : Université de Caen Normandie
ID : UNICAEN
Organisme : Région Normandie
ID : Région Normandie
Organisme : Archade
ID : Archade
Références
Science. 1997 Jul 4;277(5322):55-60
pubmed: 9204896
Nat Rev Cancer. 2008 Aug;8(8):592-603
pubmed: 18650835
Neurochem Res. 2017 Feb;42(2):625-633
pubmed: 27885577
Cancer Invest. 2016;34(1):39-44
pubmed: 26735326
Oncotarget. 2014 Apr 30;5(8):2208-20
pubmed: 24809734
Nat Rev Neurosci. 2007 Aug;8(8):610-22
pubmed: 17643088
J Clin Invest. 2010 Mar;120(3):694-705
pubmed: 20179352
J Clin Invest. 2017 Feb 1;127(2):415-426
pubmed: 28145904
Brain Pathol. 2005 Oct;15(4):311-7
pubmed: 16389943
Cancer Res. 2010 Jul 15;70(14):5679-85
pubmed: 20631066
Nat Rev Cancer. 2020 Apr;20(4):203-217
pubmed: 32161398
Mol Ther. 2012 May;20(5):1046-55
pubmed: 22334019
Proc Natl Acad Sci U S A. 2016 Apr 19;113(16):4476-81
pubmed: 27044098
Cancer Cell. 2011 Apr 12;19(4):512-26
pubmed: 21481792
PLoS One. 2020 Apr 2;15(4):e0226444
pubmed: 32240177
Cancers (Basel). 2019 Mar 06;11(3):
pubmed: 30845704
J Immunol. 2007 Jun 1;178(11):7405-11
pubmed: 17513791
Cancer Res. 2010 Jul 1;70(13):5270-80
pubmed: 20530679
Neoplasia. 2006 May;8(5):419-28
pubmed: 16790091
EMBO Mol Med. 2015 Dec 14;8(1):39-57
pubmed: 26666269
Neuro Oncol. 2013 Aug;15(8):1079-87
pubmed: 23828240
Oncotarget. 2016 Mar 29;7(13):16146-57
pubmed: 26910374
Lancet Oncol. 2009 May;10(5):459-66
pubmed: 19269895
Blood. 2007 Jun 15;109(12):5276-85
pubmed: 17327411
Am J Pathol. 1998 Nov;153(5):1459-66
pubmed: 9811337
Nat Rev Immunol. 2007 Oct;7(10):803-15
pubmed: 17893694
Oncoimmunology. 2019 Apr 13;8(7):1596004
pubmed: 31143517
Am J Nephrol. 2010;31(6):490-500
pubmed: 20453494
Neuro Oncol. 2009 Oct;11(5):488-502
pubmed: 19168695
Cancer Immunol Res. 2019 Dec;7(12):1910-1927
pubmed: 31597643
FASEB J. 2005 Jun;19(8):963-5
pubmed: 15802489
N Engl J Med. 2014 Feb 20;370(8):699-708
pubmed: 24552317
Neuro Oncol. 2014 Jul;16(7):896-913
pubmed: 24842956
Acta Neuropathol. 1987;74(3):269-77
pubmed: 3314311
Oncoimmunology. 2015 Jun 5;5(1):e1056442
pubmed: 26942063
Sci Rep. 2019 Jul 31;9(1):11085
pubmed: 31366997
Genome Integr. 2011 Aug 11;2(1):7
pubmed: 21834983
Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9363-7
pubmed: 7568133
Neuro Oncol. 2017 Oct 19;19(11):1435-1446
pubmed: 28575312
Proc Natl Acad Sci U S A. 2016 Apr 19;113(16):4470-5
pubmed: 27044097
Blood. 2005 Feb 15;105(4):1523-30
pubmed: 15498854
Acta Neuropathol. 2016 Jun;131(6):803-20
pubmed: 27157931
Nat Methods. 2012 Jul;9(7):671-5
pubmed: 22930834
Cancer Res. 2001 Aug 15;61(16):6248-54
pubmed: 11507079
Exp Cell Res. 2006 Aug 15;312(14):2641-6
pubmed: 16893723
Am J Pathol. 2004 Nov;165(5):1557-70
pubmed: 15509526
J Immunol. 2011 Apr 1;186(7):4183-90
pubmed: 21368233
Ann N Y Acad Sci. 2015 Jul;1347:45-51
pubmed: 25773744
Int J Mol Sci. 2018 Mar 17;19(3):
pubmed: 29562589
N Engl J Med. 2005 Mar 10;352(10):987-96
pubmed: 15758009
Cancer Cell. 2016 Dec 12;30(6):953-967
pubmed: 27960088
Circ Res. 1998 Oct 19;83(8):852-9
pubmed: 9776732
N Engl J Med. 2014 Feb 20;370(8):709-22
pubmed: 24552318