Effect of thalidomide affecting VEGF secretion, cell migration, adhesion and capillary tube formation of human endothelial EA.hy 926 cells.
Angiogenesis, new blood vessel formation, is a multistep process, precisely regulated by pro-angiogenic cytokines, which stimulate endothelial cells to migrate, proliferate and differentiate to form new capillary microvessels. Excessive vascular development and blood vessel remodeling appears in psoriasis, rheumatoid arthritis, diabetic retinopathy and solid tumors formation. Thalidomide [alpha-(N-phthalimido)-glutarimide] is known to be a potent inhibitor of angiogenesis, but the mechanism of its inhibitory action remains unclear. The aim of the study was to investigate the potential influence of thalidomide on the several steps of angiogenesis, using in vitro models. We have evaluated the effect of thalidomide on VEGF secretion, cell migration, adhesion as well as in capillary formation of human endothelial cell line EA.hy 926. Thalidomide at the concentrations of 0.01 microM and 10 microM inhibited VEGF secretion into supernatants, decreased the number of formed capillary tubes and increased cell adhesion to collagen. Administration of thalidomide at the concentration of 0.01 microM increased cell migration, while at 10 microM, it decreased cell migration. Thalidomide in concentrations from 0.1 microM to 10 microM did not change cell proliferation of 72-h cell cultures. We conclude that anti-angiogenic action of thalidomide is due to direct inhibitory action on VEGF secretion and capillary microvessel formation as well as immunomodulatory influence on EA.hy 926 cells migration and adhesion.
Komorowski
Jan
J
Department of Clinical Endocrinology, Chair of Endocrinology, Medical University of Lodz Dr Sterling 3 Street, 91-425 Lodz, Poland.
Jerczyńska
Hanna
H
Siejka
Agnieszka
A
Barańska
Patrycja
P
Ławnicka
Hanna
H
Pawłowska
Zofia
Z
Stepień
Henryk
H
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D002196:Capillaries / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D006801:Humans; D013792:Thalidomide / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D020533:Angiogenesis Inhibitors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D013792:Thalidomide