The angiopoietin/Tie2 axis mediates malignant pleural effusion formation
Charalampos Moschos1, Ioannis Psallidas, Androniki Kollintza
1Applied Biomedical Research & Training Center Marianthi Simou, 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 microl and 316 +/- 62 microl 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.
Insights
Blocking the angiopoietin/Tie2 axis significantly reduced malignant pleural effusion (MPE) fluid and tumor growth in mice. This pathway is crucial in MPE development, suggesting potential therapeutic targets.
Area of Science:
- Oncology
- Vascular Biology
- Immunology
Background:
- Angiopoietins and Tie2 receptor are key in angiogenesis, vascular permeability, and inflammation.
- These processes are central to the pathogenesis of malignant pleural effusions (MPEs).
Purpose of the Study:
- To investigate the role of the angiopoietin/Tie2 axis in the development of MPEs.
- To evaluate the therapeutic potential of targeting this axis in MPE models.
Main Methods:
- MPE was induced in C57BL/6 mice using intrapleural adenocarcinoma cells.
- Mice received intraperitoneal injections of MuTekdeltaFc (a soluble Tie2 receptor) or vehicle control.
- MuTekdeltaFc disrupts angiopoietin-Tie2 interactions.
Main Results:
- Treatment significantly reduced pleural fluid volume and pleural tumor foci by over 40%.
- Blockade downregulated tumor angiogenesis, vascular permeability, inflammation, and VEGF/IL-6 levels.
- Tumor cell apoptosis was induced in treated animals.
Conclusions:
- The angiopoietin/Tie2 axis plays a significant role in MPE pathogenesis.
- Targeting this pathway warrants further investigation for MPE treatment in patients.
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