Τίτλος:
Role of angiopoietins in mesothelioma progression
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. © 2018 Elsevier Ltd
Συγγραφείς:
Magkouta, S.
Kollintza, A.
Moschos, C.
Spella, M.
Skianis, I.
Pappas, A.
Vazakidou, M.-E.
Stathopoulos, G.
Kalomenidis, I.
Εκδότης:
INSTAP Academic Press
Λέξεις-κλειδιά:
angiopoietin; angiopoietin 1; angiopoietin 2; messenger RNA; platelet endothelial cell adhesion molecule 1; vasculotropin; angiopoietin 1; angiopoietin 2; messenger RNA; platelet endothelial cell adhesion molecule 1; vasculotropin A, AB1 cell line; AE17 cell line; animal cell; animal experiment; animal model; animal tissue; Article; cancer growth; carcinogenesis; CDH5 gene; controlled study; disease association; enzyme mechanism; epithelioid cell; gene expression; human; in vivo study; mesothelioma; mesothelioma cell line; mouse; nonhuman; oncogene; pathophysiology; priority journal; protein expression; RNA sequence; tumor promotion; tumor vascularization; animal; Bagg albino mouse; C57BL mouse; disease exacerbation; female; male; mesothelioma; metabolism; neovascularization (pathology); pathology; physiology; signal transduction, Angiopoietin-1; Angiopoietin-2; Animals; Disease Progression; Female; Humans; Male; Mesothelioma; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Neovascularization, Pathologic; Platelet Endothelial Cell Adhesion Molecule-1; RNA, Messenger; Signal Transduction; Vascular Endothelial Growth Factor A
DOI:
10.1016/j.cyto.2018.08.006
