The Angiopoietin/Tie2 Axis Mediates Malignant Pleural Effusion Formation
PURPOSE: Angiopoietins and their receptor, Tie2, participate in angiogenesis, regulation of vascular permeability, and inflammation, all central to the pathogenesis of malignant pleural effusions (MPEs). In the present study, we aimed to examine the role of the angiopoietin/Tie2 axis in MPE pathoge...
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Series: | Neoplasia: An International Journal for Oncology Research |
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doaj-89a0243d3fbb4f75933c69faa279d30e2020-11-24T23:21:31ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022009-03-0111329830410.1593/neo.81480The Angiopoietin/Tie2 Axis Mediates Malignant Pleural Effusion FormationCharalampos Moschos0Ioannis Psallidas1Androniki Kollintza2Sophia Karabela3Andreas Papapetropoulos4Spyros Papiris5Richard W. Light6Charis Roussos7Georgios T. Stathopoulos8Ioannis Kalomenidis9Applied Biomedical Research & Training Center “Marianthi Simou” and “George P. Livanos” Laboratory Athens GreeceApplied Biomedical Research & Training Center “Marianthi Simou” and “George P. Livanos” Laboratory Athens GreeceApplied Biomedical Research & Training Center “Marianthi Simou” and “George P. Livanos” Laboratory Athens GreeceApplied Biomedical Research & Training Center “Marianthi Simou” and “George P. Livanos” Laboratory Athens GreeceDepartment of Molecular Pharmacology, University of Patras Patras GreeceApplied Biomedical Research & Training Center “Marianthi Simou” and “George P. Livanos” Laboratory Athens GreeceDivision of Allergy, Pulmonary, & Critical Care Medicine, Vanderbilt University School of Medicine Nashville TN USAApplied Biomedical Research & Training Center “Marianthi Simou” and “George P. Livanos” Laboratory Athens GreeceApplied Biomedical Research & Training Center “Marianthi Simou” and “George P. Livanos” Laboratory Athens GreeceApplied Biomedical Research & Training Center “Marianthi Simou” and “George P. Livanos” Laboratory Athens Greece PURPOSE: Angiopoietins and their receptor, Tie2, participate in angiogenesis, regulation of vascular permeability, and inflammation, all central to the pathogenesis of malignant pleural effusions (MPEs). In the present study, we aimed to examine the role of the angiopoietin/Tie2 axis in MPE pathogenesis. EXPERIMENTAL DESIGN: MPE was induced by intrapleural injection of murine adenocarcinoma cells in C57BL/6 mice. Animals were given twice-weekly intraperitoneal injections of 40 mg/kg MuTekdeltaFc or vehicle. MuTekdeltaFc is a soluble Tie2 (sTie2) receptor that binds murine angiopoietins thereby disrupting their interaction with Tie2 receptors expressed on tissues. Animals were killed on day 14. RESULTS: Angiopoietin/Tie2 axis blockade significantly reduced pleural fluid volume and pleural tumor foci. The mean ± SEM pleural fluid volumes were 617 ± 48 μl and 316 ± 62 μl for the control and treated groups, respectively (P = .001), whereas the mean ± SEM tumor foci were 7.3 ± 1.0 and 3.0 ± 0.52 for the control and treated groups, respectively (P = .001). In addition, tumor-associated cachexia, tumor angiogenesis, pleural vascular permeability, recruitment of inflammatory cells to the pleural cavity, and local elaboration of vascular endothelial growth factor and interleukin 6 were also downregulated, and tumor cell apoptosis was induced in animals treated with the inhibitor. CONCLUSIONS: Our results indicate that the angiopoietin/Tie2 axis is an important component of MPE pathogenesis. Further studies are required to determine whether therapeutic interventions targeting this pathway could be beneficial for patients with MPE. http://www.sciencedirect.com/science/article/pii/S1476558609801267 |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Charalampos Moschos Ioannis Psallidas Androniki Kollintza Sophia Karabela Andreas Papapetropoulos Spyros Papiris Richard W. Light Charis Roussos Georgios T. Stathopoulos Ioannis Kalomenidis |
spellingShingle |
Charalampos Moschos Ioannis Psallidas Androniki Kollintza Sophia Karabela Andreas Papapetropoulos Spyros Papiris Richard W. Light Charis Roussos Georgios T. Stathopoulos Ioannis Kalomenidis The Angiopoietin/Tie2 Axis Mediates Malignant Pleural Effusion Formation Neoplasia: An International Journal for Oncology Research |
author_facet |
Charalampos Moschos Ioannis Psallidas Androniki Kollintza Sophia Karabela Andreas Papapetropoulos Spyros Papiris Richard W. Light Charis Roussos Georgios T. Stathopoulos Ioannis Kalomenidis |
author_sort |
Charalampos Moschos |
title |
The Angiopoietin/Tie2 Axis Mediates Malignant Pleural Effusion Formation |
title_short |
The Angiopoietin/Tie2 Axis Mediates Malignant Pleural Effusion Formation |
title_full |
The Angiopoietin/Tie2 Axis Mediates Malignant Pleural Effusion Formation |
title_fullStr |
The Angiopoietin/Tie2 Axis Mediates Malignant Pleural Effusion Formation |
title_full_unstemmed |
The Angiopoietin/Tie2 Axis Mediates Malignant Pleural Effusion Formation |
title_sort |
angiopoietin/tie2 axis mediates malignant pleural effusion formation |
publisher |
Elsevier |
series |
Neoplasia: An International Journal for Oncology Research |
issn |
1476-5586 1522-8002 |
publishDate |
2009-03-01 |
description |
PURPOSE: Angiopoietins and their receptor, Tie2, participate in angiogenesis, regulation of vascular permeability, and inflammation, all central to the pathogenesis of malignant pleural effusions (MPEs). In the present study, we aimed to examine the role of the angiopoietin/Tie2 axis in MPE pathogenesis. EXPERIMENTAL DESIGN: MPE was induced by intrapleural injection of murine adenocarcinoma cells in C57BL/6 mice. Animals were given twice-weekly intraperitoneal injections of 40 mg/kg MuTekdeltaFc or vehicle. MuTekdeltaFc is a soluble Tie2 (sTie2) receptor that binds murine angiopoietins thereby disrupting their interaction with Tie2 receptors expressed on tissues. Animals were killed on day 14. RESULTS: Angiopoietin/Tie2 axis blockade significantly reduced pleural fluid volume and pleural tumor foci. The mean ± SEM pleural fluid volumes were 617 ± 48 μl and 316 ± 62 μl for the control and treated groups, respectively (P = .001), whereas the mean ± SEM tumor foci were 7.3 ± 1.0 and 3.0 ± 0.52 for the control and treated groups, respectively (P = .001). In addition, tumor-associated cachexia, tumor angiogenesis, pleural vascular permeability, recruitment of inflammatory cells to the pleural cavity, and local elaboration of vascular endothelial growth factor and interleukin 6 were also downregulated, and tumor cell apoptosis was induced in animals treated with the inhibitor. CONCLUSIONS: Our results indicate that the angiopoietin/Tie2 axis is an important component of MPE pathogenesis. Further studies are required to determine whether therapeutic interventions targeting this pathway could be beneficial for patients with MPE.
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url |
http://www.sciencedirect.com/science/article/pii/S1476558609801267 |
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