Role of angiopoietins in mesothelioma progression.
Angiopoietin-1
/ metabolism
Angiopoietin-2
/ metabolism
Animals
Disease Progression
Female
Humans
Male
Mesothelioma
/ metabolism
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Neovascularization, Pathologic
/ metabolism
Platelet Endothelial Cell Adhesion Molecule-1
/ metabolism
RNA, Messenger
/ metabolism
Signal Transduction
/ physiology
Vascular Endothelial Growth Factor A
/ metabolism
Angiopoietins
Mesothelioma
Tumor angiogenesis
Journal
Cytokine
ISSN: 1096-0023
Titre abrégé: Cytokine
Pays: England
ID NLM: 9005353
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
22
06
2018
revised:
03
08
2018
accepted:
08
08
2018
pubmed:
12
9
2018
medline:
9
7
2020
entrez:
12
9
2018
Statut:
ppublish
Résumé
Anti-angiogenic treatment has been recently shown to be clinically beneficial for mesothelioma patients. Angiopoietins-1 and -2 are key regulators of tumor angiogenesis. Ang-1 is mainly known to promote angiogenesis and vessel stability, while Ang-2 could serve as an antagonist of Ang-1 causing vessel regression and destabilization or enhance angiogenesis in a context-dependent manner. We hypothesized that Ang-1 would promote and Ang2 would halt experimental mesothelioma by affecting tumor angiogenesis. To examine the effects of angiopoietins in mesothelioma angiogenesis and in vivo growth we constructed Ang-1 or Ang-2 overexpressing AE17 and AB1 mesothelioma cells and implanted them in the respective syngeneic animals. We also explored the clinical relevance of our observations using the human tumoral mRNAseq data available in the TCGA database. Ang-1 promotes mesothelioma angiogenesis and growth while the effect of Ang-2 is context-dependent. Low Ang-1 levels in human mesotheliomas are associated with the epitheloid subtype. Tumors of high Ang-1, or concurrent high Ang-2 and VEGF expression present high PECAM-1 and CDH5 expression, markers of vascularity and vascular stability, respectively. Our results highlight the importance of angiopoietins in mesothelioma pathophysiology and pave the way for the clinical development of novel anti-angiogenic strategies.
Sections du résumé
BACKGROUND AND OBJECTIVE
Anti-angiogenic treatment has been recently shown to be clinically beneficial for mesothelioma patients. Angiopoietins-1 and -2 are key regulators of tumor angiogenesis. Ang-1 is mainly known to promote angiogenesis and vessel stability, while Ang-2 could serve as an antagonist of Ang-1 causing vessel regression and destabilization or enhance angiogenesis in a context-dependent manner. We hypothesized that Ang-1 would promote and Ang2 would halt experimental mesothelioma by affecting tumor angiogenesis.
METHODS
To examine the effects of angiopoietins in mesothelioma angiogenesis and in vivo growth we constructed Ang-1 or Ang-2 overexpressing AE17 and AB1 mesothelioma cells and implanted them in the respective syngeneic animals. We also explored the clinical relevance of our observations using the human tumoral mRNAseq data available in the TCGA database.
RESULTS AND CONCLUSIONS
Ang-1 promotes mesothelioma angiogenesis and growth while the effect of Ang-2 is context-dependent. Low Ang-1 levels in human mesotheliomas are associated with the epitheloid subtype. Tumors of high Ang-1, or concurrent high Ang-2 and VEGF expression present high PECAM-1 and CDH5 expression, markers of vascularity and vascular stability, respectively. Our results highlight the importance of angiopoietins in mesothelioma pathophysiology and pave the way for the clinical development of novel anti-angiogenic strategies.
Identifiants
pubmed: 30201261
pii: S1043-4666(18)30341-7
doi: 10.1016/j.cyto.2018.08.006
pii:
doi:
Substances chimiques
Angiopoietin-1
0
Angiopoietin-2
0
Platelet Endothelial Cell Adhesion Molecule-1
0
RNA, Messenger
0
Vascular Endothelial Growth Factor A
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
99-106Informations de copyright
Copyright © 2018 Elsevier Ltd. All rights reserved.