Differential involvement of TGF-beta1 in mediating the motogenic effects of TSP-1 on endothelial cells, fibroblasts and oral tumour cells.
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.
Motegi
Katsumi
K
Unit of Cell and Molecular Biology, Dental School, University of Dundee, Dundee DD14HN, UK.
Harada
Koji
K
Ohe
Go
G
Jones
Sarah J
SJ
Ellis
Ian R
IR
Crouch
Dorothy H
DH
Schor
Seth L
SL
Schor
Ana M
AM
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002277:Carcinoma / Q000473:pathology*; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000276:immunology; D009062:Mouth Neoplasms / Q000473:pathology*; D019700:Thrombospondin 1 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology / Q000502:physiology*
D000906:Antibodies; D039302:Integrin alphaVbeta3; D019700:Thrombospondin 1; D053773:Transforming Growth Factor beta1; D005346:Fibroblast Growth Factors