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PMID:18555217

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Citation

Motegi, K, Harada, K, Ohe, G, Jones, SJ, Ellis, IR, Crouch, DH, Schor, SL and Schor, AM (2008) Differential involvement of TGF-beta1 in mediating the motogenic effects of TSP-1 on endothelial cells, fibroblasts and oral tumour cells. Exp. Cell Res. 314:2323-33

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 microg/ml) and inhibition at high concentrations (25-100 microg/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 5-25 microg/ml and no inhibitory effect was observed. These effects were partly neutralised by antibodies to alphavbeta3 integrin. TGF-beta1 (0.1-200 ng/ml tested) mimicked the effects of TSP-1 on cell migration. Function-neutralising antibodies to TGF-beta1 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-beta1 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-beta1, whereas the effects on fibroblast and tumour cell migration are TGF-beta1-independent.

Links

PubMed Online version:10.1016/j.yexcr.2008.04.013

Keywords

Animals; Antibodies/pharmacology; Carcinoma/pathology; Cattle; Cell Adhesion/drug effects; Cell Movement/drug effects; Cells, Cultured; Endothelial Cells/drug effects; Endothelial Cells/physiology; Fibroblast Growth Factors/pharmacology; Fibroblasts/drug effects; Fibroblasts/physiology; Humans; Integrin alphaVbeta3/immunology; Mouth Neoplasms/pathology; Thrombospondin 1/antagonists & inhibitors; Thrombospondin 1/immunology; Thrombospondin 1/pharmacology; Transforming Growth Factor beta1/pharmacology; Transforming Growth Factor beta1/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:FGF2

involved_in

GO:0043537: negative regulation of blood vessel endothelial cell migration

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:FGF2

involved_in

GO:0043536: positive regulation of blood vessel endothelial cell migration

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TGFB1

involved_in

GO:0050921: positive regulation of chemotaxis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TGFB1

involved_in

GO:0043537: negative regulation of blood vessel endothelial cell migration

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TGFB1

involved_in

GO:0043536: positive regulation of blood vessel endothelial cell migration

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TGFB1

involved_in

GO:0010763: positive regulation of fibroblast migration

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TSP1

involved_in

GO:0050921: positive regulation of chemotaxis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TSP1

involved_in

GO:0043537: negative regulation of blood vessel endothelial cell migration

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TSP1

involved_in

GO:0043536: positive regulation of blood vessel endothelial cell migration

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TSP1

involved_in

GO:0030511: positive regulation of transforming growth factor beta receptor signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TSP1

involved_in

GO:0016477: cell migration

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TSP1

involved_in

GO:0010763: positive regulation of fibroblast migration

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TSP1

involved_in

GO:0010596: negative regulation of endothelial cell migration

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TSP1

involved_in

GO:0010595: positive regulation of endothelial cell migration

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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