Effects of thalidomide on parameters involved in angiogenesis: an in vitro study.
In an attempt to elucidate the mechanism(s) of action of thalidomide, a reportedly antiangiogenic molecule recently tested in the treatment of relapsing malignant gliomas, we performed an in vitro study on the following parameters: (a) effect of thalidomide on proliferation of endothelial cells; (b) effect of thalidomide on expression of alpha(v)beta3 integrin on the surface of endothelial cells; (c) effect of thalidomide on the release by endothelial cells of MMP-2, IL-8 and TNF-alpha. The results show that thalidomide inhibits endotelial cell proliferation induced by bFGF and VEGF, more so if the cells are grown on vitronectin; moreover, treatment with thalidomide reduces the release of MMP-2 and IL-8 by endothelial cells, suggesting a further pathway for the antiangiogenic activity of drug. On the other hand, thalidomide does not modify expression of alpha(v)beta3 on endothelial cells.
Gelati
M
M
Istituto Nazionale Neurologico C. Besta, Milan, Italy.
Corsini
E
E
Frigerio
S
S
Pollo
B
B
Broggi
G
G
Croci
D
D
Silvani
A
A
Boiardi
A
A
Salmaggi
A
A
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016228:Endothelial Growth Factors / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000502:physiology; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D016209:Interleukin-8 / Q000378:metabolism; D008222:Lymphokines / Q000502:physiology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011956:Receptors, Cell Surface / Q000378:metabolism; D013792:Thalidomide / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D019096:Vitronectin / Q000502:physiology
D020533:Angiogenesis Inhibitors; D016228:Endothelial Growth Factors; D039302:Integrin alphaVbeta3; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; D008222:Lymphokines; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D019096:Vitronectin; D016222:Fibroblast Growth Factor 2; D013792:Thalidomide; D020778:Matrix Metalloproteinase 2