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.
Department of General Surgery, University Hospital and Medical School, University of Crete, Greece.
T
T
Vrekoussis
E N
EN
Stathopoulos
U
U
De Giorgi
M
M
Kafousi
K
K
Pavlaki
A
A
Kalogeraki
E
E
Chrysos
G
G
Fiorentini
O
O
Zoras
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