Role of angiopoietins in mesothelioma progression
| Autor: | Maria-Eleni Vazakidou, Androniki Kollintza, Sophia Magkouta, Ioannis Kalomenidis, Ioannis Skianis, M Spella, Georgios T. Stathopoulos, Charalampos Moschos, Apostolos Pappas |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Mesothelioma Vascular Endothelial Growth Factor A 0301 basic medicine Tumor angiogenesis Angiogenesis Immunology Biochemistry Angiopoietin-2 Mice 03 medical and health sciences 0302 clinical medicine Vascularity In vivo Angiopoietin-1 Animals Humans Immunology and Allergy Medicine Clinical significance RNA Messenger Molecular Biology Mice Inbred BALB C Neovascularization Pathologic business.industry Angiopoietins Hematology medicine.disease Pathophysiology Mice Inbred C57BL Platelet Endothelial Cell Adhesion Molecule-1 030104 developmental biology 030220 oncology & carcinogenesis Disease Progression cardiovascular system Cancer research Female medicine.symptom business hormones hormone substitutes and hormone antagonists Signal Transduction |
| Zdroj: | Cytokine. 118:99-106 |
| ISSN: | 1043-4666 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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