Avian Reovirus P17 Suppresses Angiogenesis by Promoting DPP4 Secretion.
Angiogenesis Inhibitors
/ pharmacology
Animals
Cell Movement
/ drug effects
Chickens
Dipeptidyl Peptidase 4
/ metabolism
Fibroblast Growth Factor 2
/ pharmacology
Human Umbilical Vein Endothelial Cells
Humans
Microvessels
/ cytology
Morphogenesis
/ drug effects
Neovascularization, Pathologic
/ metabolism
Orthoreovirus, Avian
/ metabolism
Recombinant Proteins
/ pharmacology
Transduction, Genetic
Up-Regulation
/ drug effects
Viral Nonstructural Proteins
/ pharmacology
ARV p17
DPP4
FGF-2
VEGF-A
angiogenesis
antiangiogenic activity
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
28 01 2021
28 01 2021
Historique:
received:
02
12
2020
revised:
18
01
2021
accepted:
22
01
2021
entrez:
2
2
2021
pubmed:
3
2
2021
medline:
15
10
2021
Statut:
epublish
Résumé
Avian reovirus p17 (ARV p17) is a non-structural protein known to activate autophagy, interfere with gene transcription and induce a significant tumor cell growth inhibition in vitro and in vivo. In this study, we show that ARV p17 is capable of exerting potent antiangiogenic properties. The viral protein significantly inhibited the physiological angiogenesis of human endothelial cells (ECs) by affecting migration, capillary-like structure and new vessel formation. ARV p17 was not only able to suppress the EC physiological angiogenesis but also rendered ECs insensitive to two different potent proangiogenic inducers, such as VEGF-A and FGF-2 in the three-dimensional (3D) Matrigel and spheroid assay. ARV p17 was found to exert its antiangiogenic activity by upregulating transcription and release of the well-known tumor suppressor molecule dipeptidyl peptidase 4 (DPP4). The ability of ARV p17 to impact on angiogenesis is completely new and highlights the "two compartments" activity of the viral protein that is expected to hamper the tumor parenchymal/stromal crosstalk. The complex antitumor activities of ARV p17 open the way to a new promising field of research aimed to develop new therapeutic approaches for treating tumor and cancer metastasis.
Identifiants
pubmed: 33525607
pii: cells10020259
doi: 10.3390/cells10020259
pmc: PMC7911508
pii:
doi:
Substances chimiques
Angiogenesis Inhibitors
0
Recombinant Proteins
0
Viral Nonstructural Proteins
0
Fibroblast Growth Factor 2
103107-01-3
Dipeptidyl Peptidase 4
EC 3.4.14.5
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
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