Modulation of vascular endothelium by imatinib: a study on the EA.hy 926 endothelial cell line.
In this study the EA.hy 926 endothelial cell line--simulating endothelial cells--was treated with imatinib in order to define a possible anti-angiogenic role for imatinib. Dose and time response experiments were performed. Cell morphology was studied, while migration efficiency, intercellular permeability and VE-cadherin expression were assayed, both in the presence and in the absence of imatinib. Imatinib-induced EA.hy 926 cell apoptosis was also examined. Results showed that imatinib reduced the endothelial cell population, changed cell monolayer morphology and reduced cell-to-cell cohesiveness. Migration efficiency was significantly decreased while intercellular permeability was 2.76-fold increased in the presence of imatinib. Indirect immunofluorescence microscopy showed nearly complete down-regulation of VE cadherin in imatinib-treated cells. Furthermore, apoptotic activity was detected in imatinib-treated cells. Altogether our results support an antiangiogenic profile for imatinib that possibly contributes to its therapeutic potential.
Vrekoussis
T
T
Department of General Surgery, University Hospital and Medical School, University of Crete, Greece.
Stathopoulos
E N
EN
De Giorgi
U
U
Kafousi
M
M
Pavlaki
K
K
Kalogeraki
A
A
Chrysos
E
E
Fiorentini
G
G
Zoras
O
O
D015703:Antigens, CD; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001549:Benzamides; D015820:Cadherins / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D000068877:Imatinib Mesylate; D018919:Neovascularization, Physiologic; D010879:Piperazines / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000494:pharmacology*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D000099152:Cadherin 5
D015703:Antigens, CD; D000970:Antineoplastic Agents; D001549:Benzamides; D015820:Cadherins; D000068877:Imatinib Mesylate; D010879:Piperazines; D011505:Protein-Tyrosine Kinases; D011743:Pyrimidines; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta; D000099152:Cadherin 5