Physiological concentrations of gangliosides gm1, gm2 and gm3 differentially modify basic-fibroblast-growth-factor-induced mitogenesis and the associated signalling pathway in endothelial cells
✍ Scribed by Mark Slevin; Shant Kumar; Xiaotong He; John Gaffney
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- French
- Weight
- 403 KB
- Volume
- 82
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
It has been suggested that gangliosides can influence the growth of cells by modulation of growth-factor-receptor signalling. The activation of endothelial cells (EC) during angiogenesis is crucial for tumour growth and for metastasis, also for numerous other physiological and pathological situations. Pre-treatment of bovine aortic endothelial cells (BAEC) with GM1 or GM2 (5-20 M) inhibited basic-fibroblast-growthfactor (bFGF)-induced mitogenesis, but GM3 (0.1-20 M) acted synergistically, increasing proliferation above that of bFGF alone (p F 0.05). The mitogenic effect of all 3 gangliosides was markedly reduced if the cells were washed to remove excess gangliosides from the medium before addition of bFGF. We further show that GM1 and to a lesser extent GM2 modify bFGF binding to its receptor and inhibit the associated mitogenic signal-transduction pathway of proteintyrosine phosphorylation of 40 to 120 kDa, PLC␥1, MAP kinase and protein-kinase-C activation. In contrast, GM3 increased tyrosine phosphorylation and MAP kinase activity, as compared with bFGF alone. The observed differential modulation of bFGF-induced mitogenesis by GM1, GM2 and GM3 was at concentrations routinely occurring in the serum of cancer patients. The results suggest that circulating gangliosides may have a role in regulating solid-tumour growth by modulating angiogenesis.