Abstract
The role of TSP-1 in tumour growth and angiogenesis remains controversial, with both stimulatory and inhibitory roles proposed. The effects of TSP-1 on the migration of endothelial cells, fibroblast and oral tumour cell lines were examined using the transmembrane assay. TSP-1 induced a bi-phasic effect on human and bovine endothelial cells: stimulation at low concentrations (0.1-10 mu g/ml) and inhibition at high concentrations (25-100 mu g/ml). FGF-2-stimulated endothelial cell migration was either further stimulated or inhibited by TSP-1, following the same bi-phasic dose response as in the absence of FGF-2. In contrast, TSP-1 stimulated the migration of human fibroblast and oral tumour cells in a dose dependent manner; a plateau was reached with S-2S mu g/ml and no inhibitory effect was observed. These effects were partly neutralised by antibodies to alpha v beta 3 integrin. TGF-beta 1 (0.1-200ng/ml tested) mimicked the effects of TSP-1 on cell migration. Function-neutralising antibodies to TGF-1 completely abolished both the stimulatory and inhibitory effects of TSP-1 on endothelial migration, but had no effect on TSP-1-stimulated migration of fibroblast and oral tumour cells. The effects of TGF-beta 1 were not affected by antibodies to TSP-1. These results indicate that the effects of TSP-1 on endothelial cell migration are mediated by TGF-beta 1, whereas the effects on fibroblast and tumour cell migration are TGF-beta 1-independent. (c) 2008 Elsevier Inc. All rights reserved.
Original language | English |
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Pages (from-to) | 2323-2333 |
Number of pages | 11 |
Journal | Experimental Cell Research |
Volume | 314 |
Issue number | 13 |
DOIs | |
Publication status | Published - 1 Aug 2008 |
Keywords
- TSP-1
- TGF-beta 1
- FGF-2
- alpha v beta 3
- migration
- endothelial cells
- oral tumour cells
- fibroblasts
- GROWTH-FACTOR-BETA
- HUMAN SALIVARY-GLAND
- ACTIVATOR INHIBITOR TYPE-1
- TGF-BETA
- IN-VITRO
- UP-REGULATION
- TRANSFORMING GROWTH-FACTOR-BETA-1
- MESSENGER-RNA
- CANCER-CELLS
- INTEGRIN ALPHA(V)BETA(3)