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Biphasic effect of transforming growth factor-beta 1 on in vitro angiogenesis

Published in Experimental Cell Research. 1993, vol. 204, no. 2, p. 356-363
Abstract Although the existence of an increasing number of angiogenesis-regulating cytokines is well documented, the response elicited by combinations of these cytokines is largely unknown. Using an in vitro model in which microvascular endothelial cells can be induced to form capillary-like tubes within three-dimensional collagen or fibrin gels, we have investigated the effect of transforming growth factor-beta 1 (TGF-beta 1) on basic fibroblast growth factor (bFGF)-induced and vascular endothelial growth factor (VEGF)-induced angiogenesis. Endothelial cell invasion and capillary lumen formation were inhibited by TGF-beta 1 at relatively high concentrations (5-10 ng/ml), while lower concentrations (100 pg/ml-1 ng/ml) of TGF-beta 1 potentiated the effect of bFGF- and VEGF-induced invasion. The optimal potentiating effect was observed at 200-500 pg/ml TGF-beta 1. At invasion-potentiating doses of TGF-beta 1, lumen size in fibrin gels was markedly reduced compared to that in cultures treated with bFGF alone. These results show that TGF-beta 1 exerts a biphasic effect on bFGF- and VEGF-induced angiogenesis in vitro. Our studies support the notion that the nature of the angiogenic response elicited by a specific cytokine is contextual, i.e., depends on the presence and concentration of other cytokines in the pericellular environment of the responding endothelial cell.
Keywords Adrenal Cortex/blood supplyAnimalsCattleCells, Cultured/drug effectsDose-Response Relationship, DrugDrug SynergismEndothelial Growth FactorsEndothelium, Vascular/cytology/ drug effectsFibroblast Growth Factor 2LymphokinesNeovascularization, PathologicTransforming Growth Factor beta/ pharmacologyVascular Endothelial Growth Factor AVascular Endothelial Growth Factors
PMID: 7679998
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PEPPER, Michael Sean et al. Biphasic effect of transforming growth factor-beta 1 on in vitro angiogenesis. In: Experimental Cell Research, 1993, vol. 204, n° 2, p. 356-363. doi: 10.1006/excr.1993.1043 https://archive-ouverte.unige.ch/unige:9245

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Deposited on : 2010-07-12

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