Abstract
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.
MeSH terms
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Angiogenesis Inhibitors / pharmacology*
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Cell Division / drug effects
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Cells, Cultured
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Endothelial Growth Factors / physiology
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Endothelium, Vascular / cytology
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Endothelium, Vascular / drug effects*
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Endothelium, Vascular / growth & development
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Endothelium, Vascular / metabolism
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Fibroblast Growth Factor 2 / physiology
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Humans
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Integrin alphaVbeta3 / metabolism
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Intercellular Signaling Peptides and Proteins / physiology
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Interleukin-8 / metabolism
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Lymphokines / physiology
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Matrix Metalloproteinase 2 / metabolism
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Neovascularization, Pathologic / prevention & control
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Neovascularization, Physiologic / drug effects*
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Receptors, Cell Surface / metabolism
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Thalidomide / pharmacology*
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Tumor Necrosis Factor-alpha / metabolism
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Umbilical Veins / cytology
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
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Vitronectin / physiology
Substances
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Angiogenesis Inhibitors
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Endothelial Growth Factors
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Integrin alphaVbeta3
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Intercellular Signaling Peptides and Proteins
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Interleukin-8
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Lymphokines
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Receptors, Cell Surface
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Tumor Necrosis Factor-alpha
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
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Vitronectin
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Fibroblast Growth Factor 2
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Thalidomide
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Matrix Metalloproteinase 2